CN109771428A - Celastrol combines application of the erastin in the drug for the treatment of non-small cell lung cancer - Google Patents
Celastrol combines application of the erastin in the drug for the treatment of non-small cell lung cancer Download PDFInfo
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- CN109771428A CN109771428A CN201910088453.7A CN201910088453A CN109771428A CN 109771428 A CN109771428 A CN 109771428A CN 201910088453 A CN201910088453 A CN 201910088453A CN 109771428 A CN109771428 A CN 109771428A
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Abstract
The invention discloses application of the Celastrol joint erastin in the drug for the treatment of non-small cell lung cancer.The present invention experiments have shown that, after 1-5 μM of Celastrol and 1.25-5 μM of erastin Combined Treatment non-small cell lung cancer cell, it can significantly induce cancer cell that cell death occurs, reduce the survival rate of lung carcinoma cell, to reach the effect for the treatment of lung cancer, important thinking is provided in terms of lung cancer clinical treatment.
Description
Technical field
The present invention relates to application of the Celastrol joint erastin in the drug for the treatment of non-small cell lung cancer, belong to
Field of medicaments.
Background technique
Lung cancer is one of most common malignant tumour in the world, has become China's urban population Death Cause for Malignant Tumors
1st.Non-small cell type lung cancer includes squamous cell carcinoma (squamous carcinoma), gland cancer, large cell carcinoma, its cancer cell compared with small cell carcinoma
Growth division is slower, and diffusion transfer is relatively late.Non-small cell lung cancer accounts for about the 80% of all lung cancer, about 75% Finding case
When be in middle and advanced stage, survival rate is very low within 5 years.
2012, scientist had found a kind of new cell death mode dependent on iron ion, and referred to as iron is dead
(ferroptosis).Iron death morphology, biochemistry and in terms of be different from Apoptosis, meronecrosis
And cell autophagy, it is mainly characterized by mitochondria shrinkage reduction, the double-deck film density increases, and mitochondrial cristae is reduced or disappeared, while companion
There are cytoplasm and lipid active oxygen (ROS) to increase.It proves at present, iron death and tumor suppression, neuronal degeneration, antiviral immunity
A variety of physiology such as reaction and ischemia reperfusion injury and pathologic process are closely related.Therefore, the signal for furtheing investigate iron death is logical
Road and adjustment mechanism are of great significance for the treatment of related disease: on the one hand, can be dead directly by triggering or aggravating iron
Cancer cell is removed, or increases cancer cell to the sensibility of chemotherapy；On the other hand it can be restrained or delayed scarce by inhibiting iron dead
The pathogenesis such as blood-reperfusion injury, neurodegenerative disease.
As dead (ferroptosis) inducer of classical iron, erastin passes through the System Xc- for inhibiting cell,
It reduces the intake of intracellular cystine and reduces the synthesis of GSH.The decline of GSH content causes intracellular GPX4 activity to decline, and causes
Peroxidatic reaction of lipid increases, lipid ROS assembles, and finally promotes cell that iron occurs dead.Therefore, erastin induces cancer cell
Iron death, which occurs, also becomes a kind of novel strategy for the treatment of cancer.
Celastrol is a kind of quinone methyl triterpene substance, for red acicular crystal, molecular formula C29H38O4, relatively
Molecular mass is 450.61.Celastrol and qinghaosu, triptolide, capsaicine and curcumin, in 2007 by Cell
Magazine is classified as five kinds of traditional natural drug compounds for being most possibly developed as modern medicines.1936, Celastrol quilt
Scientist extracts and separates from tripterygium wilfordii root for the first time, has started the research beginning of Celastrol.According to lot of documents
Report, Celastrol have a variety of significant pharmacological activity, such as anti-inflammatory anti-oxidant, antiatherosclerosis, it is antiviral and
Neurodegenerative disease (such as Parkinson's disease, Huntington disease, Alzheimer disease).In allergic asthma, amyotrophic lateral sclerosis spinal cord side
There is potential prospect in the treatment of the diseases such as rope sclerosis, rheumatic arthritis.2006, scientist is having found Celastrol
Antitumaous effect after attempt to illustrate its anticancer mechanism, caused the research heat of Celastrol antitumaous effect and its mechanism since then
Tide.
Celastrol can influence intracellular many A signal pathways and albumen as a kind of natural proteasome inhibitor
It plays a role, such as NF- κ B, 90 HSP, proteasome, c-Jun, AKT/mTOR, VEGFR, and can induce kinds of tumor cells
Apoptosis.It clinically commonly uses it and treats lepra reaction, rheumatic arthritis and other autoimmune diseases etc..However, according to
Clinical observation and document report, Celastrol main side effects show as reproduction, endocrine and digestive system damage, especially
It is hematological system and skin and mucosa damage.The biggish toxic side effect of Celastrol limits it in clinical application.But low
Under concentration, Celastrol is not likely to produce toxic side effect, and its remarkable activity in terms of inducing apoptosis of tumour cell is not
The disconnected confirmation tested.
Therefore, the antitumor action for Celastrol how being improved in bio-safety dosage has become research hotspot, and
Celastrol is very few to the effect of the erastin iron death induced and the research of mechanism.
Summary of the invention
In view of this, the present invention provides Celastrol joint erastin in the drug for the treatment of non-small cell lung cancer
Application.The present invention is experimental material using non-small cell lung cancer cell, is conceived to tumour iron death, furthers investigate various concentration
Effect and molecular mechanism of the Celastrol to the erastin iron death induced, passing through, which reduces the poison of Celastrol, secondary makees
With while promoting cancer cell death, to provide fundamental basis to the treatment of cancer and new way.
Treat the pharmaceutical composition of non-small cell lung cancer, including following raw material: Celastrol and erastin, wherein thunder
The effective concentration of celastrol is 1-5 μM, and the effective concentration of erastin is 1.25-5 μM.
It further, further include one or more pharmaceutically acceptable drug excipients, drug excipient is cosolvent, cream
One of agent, solubilizer, osmotic pressure regulator, binder, filler, disintegrating agent, lubricant, preservative and antioxidant
Or it is a variety of.
Celastrol can influence intracellular many A signal pathways and albumen as a kind of natural proteasome inhibitor
It plays a role, the Celastrol of low concentration is not likely to produce toxic side effect, and has in terms of inducing apoptosis of tumour cell and show
Write activity.Erastin is reduced intracellular by inhibiting cystine/glutamate antiporter System Xc- on cell membrane
The intake of cystine and the synthesis for reducing GSH.The decline of GSH content causes intracellular GPX4 activity to decline, and leads to lipid peroxidation
Reaction increases, lipid ROS assembles, and finally promotes cell that iron occurs dead.1-5 μM of Celastrol with 1.25-5 μM
It after erastin Combined Treatment non-small cell lung cancer cell, can significantly induce cancer cell that cell death occurs, reduce lung carcinoma cell
Survival rate, thus reach treatment lung cancer effect.
The invention has the following advantages that
(1) pharmaceutical composition usage mode is simple and drug effect is preferable, and with the extension of action time, non-small cell lung cancer is thin
The inhibited proliferation of born of the same parents enhances；
(2) highly-safe, side effect is low, can significantly induce cancer cell that cell death occurs, reduce depositing for lung carcinoma cell
Motility rate, and any damage will not be caused to other functions of body；
(3) low in cost, it is suitble to large-scale production.
Detailed description of the invention
Fig. 1 is that CCK-8 method detects the erastin of various concentration to Non-small cell lung carcinoma cell in the embodiment of the present invention 1
The influence diagram of vigor；
Fig. 2 is that the Celastrol of CCK-8 method detection various concentration in the embodiment of the present invention 2 is thin to Non-small cell lung carcinoma
The influence diagram of born of the same parents' vigor；
Fig. 3 is that CCK-8 method detects erastin and Celastrol while handling non-to people small thin in the embodiment of the present invention 3
The influence diagram of born of the same parents' lung carcinoma cell vigor；
Fig. 4 is that processing is non-to people small simultaneously for Flow cytometry erastin and Celastrol in the embodiment of the present invention 4
The influence diagram of ROS level in cell lung cancer cell；
Fig. 5 is to observe erastin and Celastrol in the embodiment of the present invention 5 while handling thin to Non-small cell lung carcinoma
The influence diagram of born of the same parents' form；
Fig. 6 is that observation erastin combines Celastrol inhibition non-small cell lung cancer nude mice model in the embodiment of the present invention 6
The influence diagram of tumor growth；
Fig. 7 is that observation erastin combines Celastrol inhibition non-small cell lung cancer nude mice model in the embodiment of the present invention 6
The histogram of tumor growth；
Specific embodiment
Following will be combined with the drawings in the embodiments of the present invention, and technical solution in the embodiment of the present invention carries out clear, complete
Site preparation description, it is clear that described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.It is based on
Embodiment in the present invention, it is obtained by those of ordinary skill in the art without making creative efforts every other
Embodiment shall fall within the protection scope of the present invention.
Embodiment 1
CCK-8 method detects influence of the erastin to Non-small cell lung carcinoma cell viability
Experimental principle
Contain WST-8 (chemical name: 2- (2- methoxyl group -4- nitrobenzophenone) -3- (4- nitrobenzophenone) -5- in CCK-8 reagent
(2,4- disulfonic acid benzene) -2H- tetrazolium monosodium salt) it is a kind of compound similar to MTT, it is in electronics coupled reagent 1- methoxy
Under base -5- toluphenazine dimethyl suflfate (1-Methoxy PMS) existence condition, it can be restored by Intramitochondrial dehydrogenase
For the orange-yellow first a ceremonial jade-ladle, used in libation product Formazan (referring to Fig. 1) with high water soluble, the Formazan quantity and living cells of generation
Quantity it is directly proportional.Therefore cell Proliferation and oxicity analysis can be directly carried out using this characteristic, the more cell Proliferation the faster, then
Color is deeper；Cytotoxicity is bigger, then color is more shallow.Its light absorption value, first a ceremonial jade-ladle, used in libation product are measured at 450nm wavelength with microplate reader
The amount that Formazan is formed is directly proportional to cell number.According to the absorbance value (OD value) measured, to judge living cells quantity, OD value
Bigger, cell activity is stronger.
Laboratory apparatus and material
Cell incubator (Thermo Fisher), ELX-800 microplate reader (BioTek), inverted microscope (LEICA
DMIRB), fetal calf serum (Biological Industries), DMEM (high sugar) culture medium (GIBCO), CCK-8 (MCE),
DMSO (Sigma), erastin (Selleck), 96 porocyte culture plates (NEST), (HCC827 is thin for non-small cell lung cancer cell
Born of the same parents, Shanghai cell institute, the Chinese Academy of Sciences).
Experimental procedure
Non-small cell lung cancer cell is inoculated in 96 orifice plates with the density in about 8000/hole, at 37 DEG C, 5%CO2, contain
It is cultivated in the cell incubator of the sugared culture solution of the DMEM high of 10% fetal calf serum.When cell density reaches 70-80%, ladder is added
The erastin for spending final concentration of 0,0.625,1.25,2.5,5,10,20 μM, using the cell handled through DMSO as negative control group,
Every kind of cell sets three multiple holes.After continuing culture respectively 24 hours, its form is observed under inverted microscope.Configuration contains 10%CCK-
8 culture medium is added in every hole in the form of changing liquid, is incubated in incubator and is measured 450nm absorbance after a certain period of time, detection
Influence of the erastin of various concentration to Non-small cell lung carcinoma cell viability, as a result as shown in Figure 1.
Cell survival rate is calculated as follows: cell survival rate=experimental group OD value/blank control group OD value × 100%；Number
It is indicated according to statistics with mean ± standard deviation (x ± s), is examined using t.
As shown in Figure 1, with the increase of erastin concentration, the survival rate of non-small cell lung cancer cell is gradually decreased, IC
50 values are 6.263 μM.As a result illustrate that erastin can reduce the survival rate of non-small cell lung cancer cell, and this survival rate is in
Concentration dependent reduces.
Embodiment 2
CCK-8 method detects influence of the Celastrol to Non-small cell lung carcinoma cell viability
Experimental principle: with embodiment 1
Laboratory apparatus and material
Cell incubator (Thermo Fisher), ELX-800 microplate reader (BioTek), inverted microscope (LEICA
DMIRB), fetal calf serum (Biological Industries), DMEM (high sugar) culture medium (GIBCO), CCK-8 (MCE),
DMSO (Sigma), Celastrol (Sigma), 96 porocyte culture plates (NEST), (HCC827 is thin for non-small cell lung cancer cell
Born of the same parents, Shanghai cell institute, the Chinese Academy of Sciences).
Experimental procedure
Non-small cell lung cancer cell is inoculated in 96 orifice plates with the density in about 8000/hole, at 37 DEG C, 5%CO2 contains
It is cultivated in the cell incubator of the sugared culture solution of the DMEM high of 10% fetal calf serum.When cell density reaches 70-80%, ladder is added
The Celastrol for spending final concentration of 0,0.625,1.25,2.5,5,10,20 μM, using the cell handled through DMSO as negative control
Group, every kind of cell set three multiple holes.After continuing culture respectively 24 hours, its form is observed under inverted microscope.Configuration contains 10%
The culture medium of CCK-8 is added in every hole in the form of changing liquid, is incubated in incubator and is measured 450nm absorbance after a certain period of time.
It is as shown in Figure 2 to detect influence result of the Celastrol of various concentration to Non-small cell lung carcinoma cell viability.
Cell survival rate is calculated as follows: cell survival rate=experimental group OD value/blank control group OD value × 100%；Number
It is indicated according to statistics with mean ± standard deviation (x ± s), is examined using t.
As shown in Figure 2, with the increase of Celastrol concentration, the survival rate of non-small cell lung cancer cell is gradually decreased,
50 value of IC is 3.812 μM.As a result illustrate that Celastrol can reduce the survival rate of non-small cell lung cancer cell, and this life
Deposit rate reduces in concentration dependent.
Embodiment 3
CCK-8 method detects the influence of erastin and Celastrol to Non-small cell lung carcinoma cell viability
Experimental principle: with embodiment 1
Laboratory apparatus and material
Cell incubator (Thermo Fisher), ELX-800 microplate reader (BioTek), inverted microscope (LEICA
DMIRB), fetal calf serum (Biological Industries), DMEM (high sugar) culture medium (GIBCO), CCK-8 (MCE),
DMSO (Sigma), erastin (Selleck), Celastrol (Sigma), 96 porocyte culture plates (NEST), non-small cell
Lung carcinoma cell (HCC827 cell, Shanghai cell institute, the Chinese Academy of Sciences).
Experimental procedure
Non-small cell lung cancer cell is inoculated in 96 orifice plates with the density in about 8000/hole, at 37 DEG C, 5%CO2 contains
It is cultivated in the cell incubator of the sugared culture solution of the DMEM high of 10% fetal calf serum.When cell density reaches 70-80%, it is added
Final concentration of 0,0.3,0.625,1.25,2.5,5 μM of the Celastrol of 2.5 μM of erastin and gradient, to be handled through DMSO
Cell be negative control group, every kind of cell sets three multiple holes.After continuing culture respectively 24 hours, it is observed under inverted microscope
Form.The culture medium containing 10%CCK-8 is configured, is added in the form of changing liquid in every hole, is incubated for after a certain period of time in incubator
Measure 450nm absorbance.Detect influence of the processing to Non-small cell lung carcinoma cell viability simultaneously of erastin and Celastrol
As a result as shown in Figure 3.
Cell survival rate is calculated as follows: cell survival rate=experimental group OD value/blank control group OD value × 100%；Number
It is indicated according to statistics with mean ± standard deviation (x ± s), is examined using t.
From the figure 3, it may be seen that handle non-small cell lung cancer simultaneously thin for 2.5 μM of erastin and 1.25-5 μM of Celastrol
When born of the same parents, cell mortality is increased in Celastrol concentration dependent.
Embodiment 4
The influence of Flow cytometry erastin and Celastrol to Non-small cell lung carcinoma intracellular ROS level
Experimental principle
Active oxygen (ROS) is the partial reduction products of oxygen during organism metabolism.ROS has important in vital movement
Effect, low-level ROS help to inhibit inflammatory reaction, promote cell Proliferation.But high-caliber ROS can promote antitumor letter
Number transduction, and induces tumor cell senescence and death.Since tumour cell needs to maintain the ROS stable state of higher level, regulate and control ROS
Anti-cancer therapies have potential application.
DCFH-DA (the bis- chlorine fluorescent proteins acetates of 2,7-) is that a kind of oxidation of the non-marking of permeable cell is quick
The fluorescence probe of sense.DCFH-DA (the bis- chlorine fluorescent proteins acetates of 2,7-) is hydrolyzed into the bis- chlorine tetrafluoros of 2,7- by cellular esterases
Double alkane (2,7- bis- chlorine fluorescins, DCFH) and DCFH is unable to permeabilized cells film, so that probe be made to be loaded in into the cell.So
Intracellular active oxygen can aoxidize non-blooming DCFH and have the DCF of fluorescence afterwards, to judge cell with fluorescence intensity
The level of interior ROS.This probe is widely used in detection cell Redox reaction.
Laboratory apparatus and material
Cell incubator (Thermo Fisher), DCFH-DA (Sigma), flow cytometer FACSCalibur (BD), tire
Cow's serum (Biological Industries), DMEM (high sugar) culture medium (GIBCO), DMSO (Sigma), erastin
(Selleck), Celastrol (Sigma), 10cm tissue culture plate (NEST), non-small cell lung cancer cell (HCC827 cell,
Shanghai cell institute, the Chinese Academy of Sciences).
Experimental procedure
By non-small cell lung cancer cell with about 2 × 106The density of a/plate is inoculated in 10cm Tissue Culture Dish, at 37 DEG C,
5%CO2, cultivate in the cell incubator of the sugared culture solution of DMEM high containing 10% fetal calf serum.When cell density reaches 70-80%
When, 2.5 μM of erastin and 1.25 μM of Celastrol is added and handles for 24 hours, using the cell handled through DMSO as negative control
Group, every kind of cell set three repetitions.It is softly washed 2-3 times after being disposed with 1 × PBS.PBS is discarded, it is dense that suitable end is added
Degree is the DCFH-DA ROS probe dilution liquid of 10uM.Cell is put back to 37 DEG C, 5%CO2 incubator is protected from light incubation.It is abandoned after 30min
Supernatant is removed, is then softly washed with 1 × PBS 2 times, extra ROS probe is washed away.Again use trypsin digestion cell, 4 DEG C of 800rpm from
Heart 3min.It after collecting cell, is softly washed with 1 × PBS 1 time, then 1 × PBS of 500ul is added in each centrifuge tube, uses liquid relief
Think highly of after being transferred to BD Calibur streaming loading pipe after outstanding cell, dyes sun with flow cytometer FL1 Air conduct measurement DCFH-DA
Property cell.Every sample will at least detect 10,000 cell, combine flow cytometry analysis software FlowJo after obtaining data
Analysis intracellular ROS level variation is calculated, and draws ROS distribution map, as a result as shown in Figure 4.
As shown in Figure 4, though 2.5 μM of erastin and 1.25 μM of Celastrol list processing can be improved slightly into the cell
ROS is horizontal, but erastin and Celastrol Combined Treatment dramatically increase the level of intracellular ROS.
Embodiment 5
Erastin and Celastrol handle the influence to Non-small cell lung carcinoma cellular morphology simultaneously
Experimental principle:
Erastin and non-small cell lung cancer cell after Celastrol Combined Treatment, observe its morphological change.
Laboratory apparatus and material
Cell incubator (Thermo Fisher), inverted microscope (Olympus), fetal calf serum (Biological
Industries), DMEM (high sugar) culture medium (GIBCO), CCK-8 (MCE), DMSO (Sigma), erastin (Selleck),
Celastrol (Sigma), 10cm Tissue Culture Dish (NEST), non-small cell lung cancer cell (HCC827 cell, Chinese Academy of Sciences Shanghai
Cell institute).
Experimental procedure
By non-small cell lung cancer cell with about 2 × 106The density of a/ware is inoculated in 10cm Tissue Culture Dish, at 37 DEG C,
5%CO2, cultivate in the cell incubator of the sugared culture solution of DMEM high containing 10% fetal calf serum.When cell density reaches 70-80%
When, 2.5 μM of erastin and 1.25 μM of Celastrol is added, using the cell handled through DMSO as negative control group.Respectively
After continuing culture 24 hours, its form is observed under inverted microscope.
Inverted microscope observation erastin and Celastrol handle the shadow to non-small cell lung cancer cell form simultaneously
It rings, as a result as shown in Figure 5.
As shown in Figure 5, when 2.5 μM of erastin and 1.25 μM of Celastrols handle cell simultaneously, cellular morphology is obvious
Change, inducing cell death.
As a result illustrate, the erastin Combined Treatment non-small cell lung cancer cell of the Celastrol of small concentration and small concentration
Afterwards, it can significantly induce cancer cell that cell death occurs, reduce the survival rate of lung carcinoma cell, to reach the effect for the treatment of lung cancer
It answers.
Embodiment 6
Erastin combines Celastrol and inhibits the growth of non-small cell lung cancer transplanted tumor in nude mice
Experimental principle:
Xenograft tumor models are established with modeling period is short, success rate is high, still retains protoplast in tumor tissues with nude mice
The features such as form and biological function of cancer, therefore nude mouse xenograft tumor model is widely used in the screening of anti-tumor drug
Occur with cancer, the clinical research of development.This experimental selection HCC827 cell is object, establishes source of people non-small cell lung cancer xenogenesis
Transplanted tumor model investigates internal inhibitory effect of the erastin of low concentration with Celastrol Combined Treatment to lung cancer.
Laboratory apparatus and material
Cell incubator (Thermo Fisher), fetal calf serum (Biological Industries), DMEM (high sugar)
Culture medium (GIBCO), erastin (Selleck), Celastrol (Sigma), 10cm Tissue Culture Dish (NEST) are non-small thin
Born of the same parents' lung carcinoma cell (HCC827 cell, Shanghai cell institute, the Chinese Academy of Sciences), BALB/c nude mice (Beijing China Fukang).
Experimental procedure
Repetitive cell incubation step cultivates sufficient cell number so as to the needs of inoculation.On the day of inoculation, collect all
Cell is diluted to 1 × 10 with PBS6A/0.2ml.Before preparing inoculation, according to 6 (SPF of weight equilibrium assignment each group male nude mouse
Grade, weight are 20 ± 2g).By non-small cell lung cancer HCC827 cell with about 1 × 106A quantity is inoculated in nude mice right hindlimb
Subcutaneously, the growth conditions and gross tumor volume of nude mice are then measured in time.When the tumor size of experiment nude mice reaches 50mm3When, sieve
Tumor size and the close nude mice of weight are selected, is divided into 4 groups: (1) model control group；(2) 5mg/kg erastin processing group；
(3) 1mg/kg Celastrol processing group；(4) 5mg/kg erastin+1mg/kg Celastrol Combined Treatment group.Model group
Give the mixed liquor of dissolution drug, the latter three groups intraperitoneal injections carried out according to weight once a day.Nude mice weight and tumour
Volume size is primary every measurement in 3 days, records and analyzes data.After drug-treated 2 weeks, implement nude mice euthanasia, dissection is taken out swollen
Tumor tissue, measurement volume record, as a result as shown in fig. 6-7.
Nude mouse tumor volume is calculated as follows: gross tumor volume (mm3)=major diameter × minor axis2×0.5。
By Fig. 6-7 it is found that compared with model group, 5mg/kg erastin or 1mg/kg Celastrol list processing group nude mice
Tumor size reduces；Compared with model group and drug list processing group, 5mg/kg erastin and 1mg/kg Celastrol joint
Tumour inhibiting rate significantly increases when processing, and the tumor size of nude mice is substantially reduced (p < 0.001).
As a result illustrate, the erastin and Celastrol Combined Treatment of small concentration can significantly inhibit HCC827 tumor-bearing mice
Tumour growth.
Claims (1)
1. Celastrol combines application of the erastin in the drug for the treatment of non-small cell lung cancer.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112472792A (en) * | 2020-12-28 | 2021-03-12 | 河北师范大学 | Application of cyclosporine A and tripterine in preparation of medicine for treating lung cancer |
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| CN101352444A (en) * | 2008-09-11 | 2009-01-28 | 中国科学院广州生物医药与健康研究院 | New use of tripterine in pharmacy |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101352444A (en) * | 2008-09-11 | 2009-01-28 | 中国科学院广州生物医药与健康研究院 | New use of tripterine in pharmacy |
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| Title |
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| CHAOLI HUANG 等: "Upregulation and activation of p53 by erastin-induced reactive oxygen species contribute to cytotoxic and cytostatic effects in A549 lung cancer cells", 《ONCOLOGY REPORTS》 * |
| 陈国柱 等: "雷公藤红素对非小细胞肺癌细胞株H1299增殖与凋亡的影响", 《生物技术通讯》 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112472792A (en) * | 2020-12-28 | 2021-03-12 | 河北师范大学 | Application of cyclosporine A and tripterine in preparation of medicine for treating lung cancer |
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