CN106668866A - Medicinal composition for resisting non-small cell lung cancer, and application thereof - Google Patents
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Abstract
The invention discloses a medicinal composition for resisting non-small cell lung cancer. The active components of the medicinal composition comprise an artemisinin derivative and EGFR-TKI (epidermal growth factor receptor-tyrosine kinase inhibitor), wherein the artemisinin derivative is selected from one of dihydroartemisinin, artesunate, artemether and arteether; and the EGFR-TKI is selected from one of gefitinib, erlotinib, afatinib and osimertinib. The invention also discloses application of the medicinal composition to preparation of medicines for treating and resisting the non-small cell lung cancer. When the medicinal composition provided by the invention is used for treating the non-small cell lung cancer, the medicinal effect which is more excellent than that of the singly used EGFR-TKI can be achieved, the sensitizing effect is achieved, the problem of partial medicine resistance of the non-small cell lung cancer EGFR-TKI is solved, and a scientific basis is provided for the development of new medicines.
Description
Technical field
The invention belongs to medical applications field, the pharmaceutical composition of more particularly to a kind of anti-nonsmall-cell lung cancer and its should
With.
Background technology
At present the M ＆ M of world community pulmonary carcinoma is united in ascendant trend year by year according to World Health Organization (WHO) WHO
Meter, the sickness rate of pulmonary carcinoma has been occupied first of malignant tumor, seriously threatens the health of the mankind.Pulmonary carcinoma can be divided into little thin by pathological
Born of the same parents' pulmonary carcinoma (small cell lung cancer, SCLC) and nonsmall-cell lung cancer (non-small cell lung cancer,
NSCLC), wherein NSCLC accounts for the 80%-90% of pulmonary carcinoma.In a very long time, advanced NSCLC patients can only receive " to contain
The chemotherapy of platinum medicine ", compared with Supporting Therapy, although adds somewhat to patients overall survival's phase, but its upper limit
It is only limitted to the 20% response rate and 8-10 median survival interval of individual month.In recent years, with the continuous progress of molecule genetics research,
NSCLC is subdivided into a variety of molecular isoforms, and the adenocarcinoma of lung for occupying NSCLC sums more than 50% can be according to associated drives
Gene mutation is further subdivided into more subgroups, and these drive gene to include EGFR, KRAS, HER2, PIK3CA, BRAF, MET
Gene mutation and ALK, ROS1 and RET gene rearrangements, and all kinds of molecular targeted therapies that have thus been born.Molecular targeted therapy
Medicine is beneficial to individualized treatment to achieve significant curative effect in NSCLC treatments the advantages of its targeting, safety.
In the exploration of targeted therapy of lung cancer, EGFR mutation drive the discovery of gene and the life of corresponding target therapeutic agent epidermis
The appearance of growth factor receptor body tyrosine kinase inhibitor (abbreviation EGFR-TKI), be advanced NSCLC treatment it is historical one in
Journey upright stone tablet event.EGFR mutation are modal driving one of genes, the EGFR especially in the non-smoking adenocarcinoma patients of asian ancestry crowd
Mutant proportion is up to 60% or so.The line EGFR-TKI of advanced NSCLC one treatments of EGFR mutation, with the double medicine chemotherapy of traditional platiniferous
Scheme is compared, and can obviously improve objective remission rate (ORR) and the progression free survival phase (PFS) of patient, it is often more important that will have
The median survival interval of the advanced NSCLC of EGFR mutation extends to 20-30 month, so EGFR-TKI is that this some patients is most important
Medicine.But it is similar to chemotherapeutics, EGFR-TKI treatments there is also resistance problems.Clinically EGFR is mutated late period
NSCLC is after EGFR-TKI first-line treatments 9-13 month, it will usually progression of disease occur because of TKI acquired drug-resistances.TKI drug resistances
Treatment after progress is the problem that doctor pays special attention in clinical practice, but also lacks the unified therapeutic scheme of standard at present.
It is annual herb plant that Herba Artemisiae Annuae belongs to Compositae also known as Herba Artemisiae annuae (Artemisia anaua L).Arteannuin is China
The Sesquiterpene lactones antimalarial agent that pharmacy worker extracts in early 1970s from Chinese medicine Herba Artemisiae Annuae, and in this structure base
On plinth again in succession synthesis, it is semi-synthetic go out a series of derivants with antimalarial active, such as dihydroarteannuin, artesunate, Hao Jia
Ether, arteether.The antimalarial active of arteannuin and its derivant has obtained universally acknowledged, with rapid-action, drug effect is high, toxic and side effects
Low advantage.In addition to antimalarial treatments are widely used in, artemisinin-based drug also has other multiple pharmacological effects, such as schistosomicide
Effect, arrhythmia, relievings asthma, antiendotoxin, the effect such as antiallergic action, lupus erythematosus, immunosuppressant.With to arteannuin
And its derivatives active research deepens continuously, disclose such compound and also there is certain antitumor action, to various swollen
The growth of oncocyte is inhibited.The Anticancer Effect and Mechanism of arteannuin and its derivant mainly has cytotoxicity, retardance
Or delay the growth cycle of tumor cell, inducing cell apoptosis, opposing angiogenesis, invasion and attack and the transfer etc. that suppress tumor.
So far, have no that relevant conjunction artemisinin derivatives and the pharmaceutical composition of EGFR-TKI are applied to anti-lung cancer
The report for the treatment of.
The content of the invention
The technical problem to be solved is for epidermal growth factor recipient tyrosine kinase inhibitor (EGFR-
TKI a kind of drug resistance defect), there is provided pharmaceutical composition of the anti-nonsmall-cell lung cancer with good synergy.
The pharmaceutical composition of anti-nonsmall-cell lung cancer of the present invention, its active component include artemisinin derivatives and
Epidermal growth factor recipient tyrosine kinase inhibitor (EGFR-TKI).
Wherein, the artemisinin derivatives can be dihydroarteannuin (DHA), artesunate (Artesunate), Artemisia
Methyl ether (Artemether), arteether (Artemotil), or its pharmaceutically useful salt, hydrate or derivant etc.；Epidermal growth factor
Sub- receptor tyrosine kinase inhibitors (EGFR-TKI) can be gefitinib (Gef), Erlotinib (Erl), Afatinib
(Afa) it is, difficult to understand uncommon for Buddhist nun (Osi), or corresponding analog, derivant.
Preferably, the artemisinin derivatives are selected from dihydroarteannuin (DHA), artesunate (Artesunate), Artemisia
One kind in methyl ether (Artemether) and arteether (Artemotil).
Its corresponding structural formula difference is as follows：
Preferably, the epidermal growth factor recipient tyrosine kinase inhibitor (EGFR-TKI) is selected from gefitinib
(Gef), Erlotinib (Erl), Afatinib (Afa) and uncommon one kind in Buddhist nun (Osi) difficult to understand.
EGFR-TKI drug resistances include primary drug resistance and secondary resistance.Primary drug resistance is referred to and use first EGFR-TKI
Treatment has no benefit, accounts for 7%-13%.Acquired drug-resistance refers to and receives curative effect occur after EGFR-TKI treatments (Tumor response, to enter
Extension is slow, symptom improves etc.) then there is progression of disease again, the mechanism of acquired drug-resistance relates generally to following aspect：EGFR bis-
Secondary mutation (such as the appearance of T790M mutation), EGFR downstream signaling molecules activation (such as PI3K/AKT, PTEN, ERK/MAPK) are other
Road activation (such as c-MET amplifications, Her-2 amplifications) and Phenotypic Change (as NSCLC is converted into SCLC).Wherein, T790M mutation and
C-MET amplifications account for more than the 50% of EGFR-TKI acquired drug-resistances, and in addition the mechanism of nearly half is completely clear and definite yet.
Find in process of the present invention, EGFR-TKI is given on the various NSCLC tumor cell lines containing EGFR mutation and is intervened
Afterwards, it is seen that significant STAT3 activation, and the activation and non-momentary, but gradually strengthen, the activation for pointing out STAT3 is a kind of anti-
Infeed mechanism.And select artemisinin derivatives effectively to suppress the phosphorylation level of STAT3 in non-small cell lung cancer cell, together
When, artemisinin derivative used has no effect on the effect that EGFR-TKI suppresses EGFR phosphorylations, can reach significant promotion
Non-small cell lung cancer cell death effect.Therefore the pharmaceutical composition of the anti-nonsmall-cell lung cancer of the present invention is used in combination arteannuin
Analog derivative blocks STAT3 feedback activation pathways as STAT3 signal pathway inhibitors, thus tackles EGFR-TKI drug resistances, rises
To the treatment curative effect of enhanced sensitivity EGFR-TKI.
Present invention test non-small cell lung cancer cell used is PC-9 and H1975, by pulmonary carcinoma association of Spain chairman
Rafael professors Rosell present.
Application of the pharmaceutical composition of above-mentioned anti-nonsmall-cell lung cancer in the anti-non-small cell lung cancer drug for the treatment of is prepared
Within the scope of the present invention.
The application refers to that described pharmaceutical composition, can in the case where not affecting EGFR-TKI to suppress EGFR phosphorylations
Effectively suppress the phosphorylation level of STAT3 in non-small cell lung cancer cell, reach the drug effect being used alone better than EGFR-TKI.
Beneficial effect：The invention provides the new pharmaceutical use of artemisinin derivatives, i.e., control as nonsmall-cell lung cancer
Sensitizer is treated, with EGFR-TKI combinations its effect of anti-lung cancer is increased.Pharmaceutical composition associated with described is not affecting EGFR-TKI
In the case of suppressing EGFR phosphorylations, can effectively suppress the phosphorylation level of STAT3 in non-small cell lung cancer cell, reach excellent
In the drug effect that EGFR-TKI is used alone, the part resistance problems of nonsmall-cell lung cancer EGFR-TKI are solved, be to develop new
Medicine provides scientific basis.
Description of the drawings
Fig. 1 is that dihydroarteannuin, artesunate, Artemether and arteether suppress PC-9 intracellular in concentration dependent
The phosphorylation of STAT3；
Fig. 2 is that dihydroarteannuin, artesunate, Artemether and arteether suppress H1975 intracellular in concentration dependent
The phosphorylation of STAT3；
Fig. 3 is that in PC-9 cells, dihydroarteannuin suppresses the STAT3 phosphorylations of EGFR-TKI induced activations；
Fig. 4 is that in H1975 cells, dihydroarteannuin suppresses the STAT3 phosphorylations of EGFR-TKI induced activations；
Fig. 5 is artemisinin derivative and EGFR-TKI acts on alone or in combination impact to PC-9 cell survival rates.
Specific embodiment
With the following Examples the invention will be further elaborated.
Experiment material：
Cell strain：Non-small cell lung cancer cell strain PC-9, H1975 are by pulmonary carcinoma association of Spain chairman Rafael
Professor Rosell presents.
Experiment reagent：Culture medium, pancreatin, mycillin and hyclone (FBS) used by cell culture is bought certainly
Life companies.Dimethyl sulfoxide (DMSO), tetrazolium bromide (MTT) are purchased from Sigma companies.All one anti-are purchased from Cell
Signaling Technology companies, the anti-labelling sheep anti mouses of DyLight 680 of Infrared fluorescence two and the labelling sheep of DyLight 800
Anti-rabbit is purchased from KPL companies.
Dihydroarteannuin (DHA), artesunate (Artesunate) be purchased from Sigma companies, Artemether (Artemether),
Arteether (Artemotil) is purchased from MedChemExpress companies.Gefitinib (Gef), Erlotinib (Erl), Afatinib
(Afa), difficult to understand wishing is purchased from Selleck companies for Buddhist nun (Osi).
Artemisinin derivative and EGFR-TKI are configured to the storing liquid of 20mmol/L with DMSO, for follow-up all of reality
Apply example.
Experiment consumptive material：All cell culture culture dishs, culture plate, centrifuge tube is purchased from Corning companies.
Embodiment 1：Artemisinin derivative suppresses STAT3 phosphorylations
Take RPMI 1640 of PC-9, H1975 cell containing 10%FBS, 100U/mL penicillins and 100 μ g/mL streptomycins
Culture medium, at 37 DEG C, 5%CO2Incubator in maintain culture.Treat that cell length, to exponential phase, uses 0.25% pancreas enzyme -EDTA
Solution digestion prepares single cell suspension, with 4 × 105The cell density of individual cells/well is inoculated with six orifice plates, after culture 24h, adds not
With the artemisinin derivative of concentration, 4 concentration are chosen altogether in IC50 values left and right, specially：20 μM, 40 μM, 60 μM, 80 μM,
DMSO is used as solvent control group.After pharmaceutical intervention 24h, remove supernatant, PBS is washed twice, add and contain protease, inhibitors of phosphatases
RIPA lysates, 30min is cracked on ice.Cell scraper collects cell lysate, and 4 DEG C, 12000r/min is centrifuged 10min.Take
Supernatant, is determined with NanoDrop 1000 and is adjusted to each sample concentration unanimously after protein concentration.Detected by Western blot is detected
The expression of EGFR, p-EGFR (Tyr1068), Stat3, p-Stat3 (Tyr705) and β-Actin.Use LI-COR
Odyssey Dual band IRs laser imaging system is imaged.
As a result such as Fig. 1 and Fig. 2 is shown, as seen from the figure, above-mentioned four kinds of artemisinin derivatives can suppress nonsmall-cell lung cancer
The phosphorylation level of the intracellular STAT3 of PC-9 and H1975.
Embodiment 2：Artemisinin derivative can suppress the STAT3 phosphorylations that EGFR-TKI is induced
Take RPMI 1640 of PC-9, H1975 cell containing 10%FBS, 100U/mL penicillins and 100ug/mL streptomycins
Culture medium, at 37 DEG C, 5%CO2Incubator in maintain culture.Treat that cell length, to exponential phase, uses 0.25% pancreas enzyme -EDTA
Solution digestion prepares single cell suspension, with 4 × 105The cell density of individual cells/well is inoculated with six orifice plates, after culture 24h, adds each
The IC50 value concentration of compound, specially：(for PC-9 cells, Gef concentration is 0.1 μM, Erl for DHA (40 μM), EGFR-TKI
Concentration is 0.1 μM, and Afa concentration is 0.0038 μM, and Osi concentration is 0.04 μM；For H1975 cells, Gef concentration is 8 μM, Erl
Concentration be 8 μM, Afa concentration be 0.3 μM, Osi concentration be 0.04 μM) or both joint, DMSO is used as solvent control group.Medicine is done
After pre- 24h, remove supernatant, PBS is washed twice, add and contain protease, the RIPA lysates of inhibitors of phosphatases, crack on ice
30min.Cell scraper collects cell lysate, and 4 DEG C, 12000r/min is centrifuged 10min.Supernatant is taken, is surveyed with NanoDrop 1000
Determine to be adjusted to each sample concentration unanimously after protein concentration.Detected by Western blot detection EGFR, p-EGFR (Tyr1068),
The expression of Stat3, p-Stat3 (Tyr705) and β-Actin.With LI-COR Odyssey Dual band IR laser imagings system
Have picture under one's command.
As a result such as Fig. 3 and Fig. 4 is shown, as seen from the figure, EGFR-TKI have activated while EGFR phosphorylations are suppressed
STAT3, but the artemisinin derivative suppression that the STAT3 of induced activation can be used in combination.Meanwhile, artemisinin derivative not shadow
Ring the effect that EGFR-TKI suppresses EGFR phosphorylations.
Embodiment 3：Artemisinin derivative cooperates with promotion non-small cell lung cancer cell dead with EGFR-TKI
RPMI1640 culture medium of the PC-9 cells containing 10%FBS, 100U/mL penicillins and 100ug/mL streptomycins is taken,
At 37 DEG C, 5%CO2Incubator in maintain culture.Treat that cell length, to exponential phase, is disappeared with 0.25% pancreas enzyme -EDTA solution
Change prepares single cell suspension, with the μ L volumes of every hole 100,2 × 103The cell concentration of individual cell is inoculated in 96 orifice plates.Culture 24h
Afterwards, respectively with the artemisinin derivative of variable concentrations, (Determination of dihydroartemisinin gradient is as follows：5、10、20、25、30、35、40、
60、80μM；Artemether Concentraton gradient is as follows：12.5、25、50、62.5、70、87.5、100、150、200μM；Arteether concentration ladder
Degree is as follows：12.5th, 25,50,62.5,70,87.5,100,150,200 μM) and the EGFR-TKI of variable concentrations (gefitinib is dense
Degree gradient is as follows：0.0125、0.025、0.05、0.0625、0.075、0.0875、0.1、0.15、0.2μM；Afatinib concentration
Gradient is as follows：0.000475、0.00095、0.0019、0.002379、0.00285、0.003325、0.0038、0.0057、
0.0076μM；Ao Xi is as follows for Buddhist nun's Concentraton gradient：0.02、0.04、0.08、0.1、0.12、0.14、0.16、0.24、0.32μM)
Intervene cell in form alone or in combination, using DMSO as solvent control group.Culture 3d after, add 10 μ L MTT (5mg/mL) after
Continuous incubation 4h, sops up supernatant, adds 100 μ L DMSO vibration 10min.With all-wave length microplate reader (Thermo Multiskan
Spectrum) detection light absorption value at wavelength 570nm and reference wavelength 630nm is being determined.According to formula：Suppression ratio=(1-
(A570nm-A630nm)treated/(A570nm-A630nm)control) × 100% calculates suppression ratio.
As a result show such as Fig. 5, as seen from the figure, in terms of PC-9 cell growths are suppressed, artemisinin derivative and EGFR-TKI
Combination be substantially better than and be administered alone, table 1 lists in above-mentioned concentration different artemisinin derivatives and difference EGFR-TKI most
Good concentration ratio.For example, by the visible Afatinib (Afa) of table 1, suppression ratio is 6.4% at 0.0019 μM, dihydroarteannuin
(DHA) at 20 μM, suppression ratio is 5.8%, and both are 33.8% by suppression ratio during this concentration administering drug combinations, is produced significant
Synergism.
Table 1
Meanwhile, according to formula：Survival rate=(A570nm-A630nm)treated/(A570nm-A630nm)control× 100% calculating is deposited
Motility rate.Using CalcuSyn computed in software drug combination indexes (Combination Index, CI), according to Chou-Talalay
Definition, CI<1 defines two medicines for cooperative effect, and CI=1 defines two medicines for synergistic effect, CI>1 defines two medicines for antagonistic effect.Survey
Surely 2 be the results are shown in Table, it can be seen that, the pharmaceutical composition of the present invention is respectively provided with cooperative effect in above-mentioned concentration.
Table 2
Claims (4)
1. a kind of pharmaceutical composition of anti-nonsmall-cell lung cancer, it is characterised in that the active component of the pharmaceutical composition includes green grass or young crops
Artemisin analog derivative and epidermal growth factor recipient tyrosine kinase inhibitor.
2. pharmaceutical composition according to claim 1, it is characterised in that the artemisinin derivatives are selected from double hydrogen Herba Artemisiae Annuaes
One kind in element, artesunate, Artemether and arteether.
3. pharmaceutical composition according to claim 1, it is characterised in that the epidermal growth factor recipient tyrosine kinase
Inhibitor is selected from gefitinib, Erlotinib, Afatinib and Ao Xi for the one kind in Buddhist nun.
4. application of arbitrary described pharmaceutical composition in the anti-non-small cell lung cancer drug for the treatment of is prepared in claim 1-3.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106727586A (en) * | 2016-12-06 | 2017-05-31 | 遵义医学院附属医院 | A kind of new opplication of Artesunate |
| CN109432086A (en) * | 2018-12-05 | 2019-03-08 | 江苏省中医药研究院 | The application of qinghaosu or derivatives thereof and the composition of EGFR-TKI targeted drug |
| CN109674990A (en) * | 2019-01-30 | 2019-04-26 | 中国人民解放军西部战区总医院 | With the composition and preparation method thereof for adjusting EGFR effect |
| US10513509B2 (en) | 2016-05-26 | 2019-12-24 | Recurium Ip Holdings, Llc | EGFR inhibitor compounds |
| CN111218424A (en) * | 2019-12-12 | 2020-06-02 | 广州医科大学附属第一医院 | Oxitinib drug-resistant cell strain NCI-H1975/AR and application thereof |
| CN112043717A (en) * | 2020-05-14 | 2020-12-08 | 青岛市肿瘤医院 | Pharmaceutical composition for treating lung cancer and preparation thereof |
| CN112773788A (en) * | 2020-09-29 | 2021-05-11 | 上海市肺科医院 | Application of dihydroartemisinin in preparation of non-small cell lung cancer medicine |
| CN113599526A (en) * | 2021-08-26 | 2021-11-05 | 清华大学深圳国际研究生院 | Application of autophagy pathway activator as EGFR TKI drug sensitizer |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103251585A (en) * | 2012-02-15 | 2013-08-21 | 中国科学院上海生命科学研究院 | Effects and application of artemisinin and its derivative in inhibition of platelet-derived growth factor receptor A |
| WO2016023090A1 (en) * | 2014-08-11 | 2016-02-18 | Fundacão Oswaldo Cruz | Phenylaminopyrimidine-derived compounds, method for producing the same, use of said compounds for the treatment of cancer, and treatment methods |
| US20160175331A1 (en) * | 2014-12-23 | 2016-06-23 | University Of Maryland, Baltimore | Treatment of leukemia with artemisinin derivatives and combinations with other antineoplastic agents |
| CN106727586A (en) * | 2016-12-06 | 2017-05-31 | 遵义医学院附属医院 | A kind of new opplication of Artesunate |
-
2017
- 2017-02-13 CN CN201710075741.XA patent/CN106668866A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103251585A (en) * | 2012-02-15 | 2013-08-21 | 中国科学院上海生命科学研究院 | Effects and application of artemisinin and its derivative in inhibition of platelet-derived growth factor receptor A |
| WO2016023090A1 (en) * | 2014-08-11 | 2016-02-18 | Fundacão Oswaldo Cruz | Phenylaminopyrimidine-derived compounds, method for producing the same, use of said compounds for the treatment of cancer, and treatment methods |
| US20160175331A1 (en) * | 2014-12-23 | 2016-06-23 | University Of Maryland, Baltimore | Treatment of leukemia with artemisinin derivatives and combinations with other antineoplastic agents |
| CN106727586A (en) * | 2016-12-06 | 2017-05-31 | 遵义医学院附属医院 | A kind of new opplication of Artesunate |
Non-Patent Citations (3)
| Title |
|---|
| 刘俊等: "EGFR-TKI 治疗非小细胞肺癌的耐药机制进展研究", 《中国肿瘤临床》 * |
| 邓立力等: "PI3K/Akt通路在EGFR/KRAS不同遗传背景NSCLC细胞对TRAIL敏感性中的作用", 《中国肿瘤》 * |
| 马虎: "青蒿琥酯对NSCLC抗瘤及增强厄洛替尼体内外抗瘤活性的实验研究", 《中国博士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10513509B2 (en) | 2016-05-26 | 2019-12-24 | Recurium Ip Holdings, Llc | EGFR inhibitor compounds |
| US11098030B2 (en) | 2016-05-26 | 2021-08-24 | Recurium Ip Holdings, Llc | EGFR inhibitor compounds |
| CN106727586A (en) * | 2016-12-06 | 2017-05-31 | 遵义医学院附属医院 | A kind of new opplication of Artesunate |
| CN109432086A (en) * | 2018-12-05 | 2019-03-08 | 江苏省中医药研究院 | The application of qinghaosu or derivatives thereof and the composition of EGFR-TKI targeted drug |
| CN109674990A (en) * | 2019-01-30 | 2019-04-26 | 中国人民解放军西部战区总医院 | With the composition and preparation method thereof for adjusting EGFR effect |
| CN111218424A (en) * | 2019-12-12 | 2020-06-02 | 广州医科大学附属第一医院 | Oxitinib drug-resistant cell strain NCI-H1975/AR and application thereof |
| CN111218424B (en) * | 2019-12-12 | 2022-04-15 | 广州医科大学附属第一医院 | Oxitinib drug-resistant cell strain NCI-H1975/AR and application thereof |
| CN112043717A (en) * | 2020-05-14 | 2020-12-08 | 青岛市肿瘤医院 | Pharmaceutical composition for treating lung cancer and preparation thereof |
| CN112043717B (en) * | 2020-05-14 | 2022-10-04 | 青岛市肿瘤医院 | Pharmaceutical composition for treating lung cancer and preparation thereof |
| CN112773788A (en) * | 2020-09-29 | 2021-05-11 | 上海市肺科医院 | Application of dihydroartemisinin in preparation of non-small cell lung cancer medicine |
| CN113599526A (en) * | 2021-08-26 | 2021-11-05 | 清华大学深圳国际研究生院 | Application of autophagy pathway activator as EGFR TKI drug sensitizer |
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