CN110151976A - Application of the ZNF496 albumen in terms of improving Chemotherapy of Cervical Cancer drug susceptibility - Google Patents
Application of the ZNF496 albumen in terms of improving Chemotherapy of Cervical Cancer drug susceptibility Download PDFInfo
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- CN110151976A CN110151976A CN201910591721.7A CN201910591721A CN110151976A CN 110151976 A CN110151976 A CN 110151976A CN 201910591721 A CN201910591721 A CN 201910591721A CN 110151976 A CN110151976 A CN 110151976A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The invention discloses a kind of application of ZNF496 albumen in terms of improving Chemotherapy of Cervical Cancer drug susceptibility.Stable transfection is distinguished using ZNF496 over-express vector and/or transiently transfects cervical cancer cell lines, and the processing for the treatment of with chemotherapy drugs Cisplatin increases induction of the cis-platinum to Hela Cell Apoptosis；Stablized by ZNF496 and is overexpressed to increase the inhibiting effect that cis-platinum is proliferated cervical cancer cell；ZNF496 can effectively enhance the inhibiting effect that cis-platinum grows cervical cancer cell in vivo.The present invention has the advantages that providing new target spot and therapeutic strategy to increase the solution of Chemotherapy of Cervical Cancer drug susceptibility problem, specific targeted therapy scheme can be designed, and it is applied to the preparation that ZNF496 is overexpressed preparation medicine, use in conjunction chemotherapeutics, accurately individualized treatment is implemented to cervical cancer patient, it is with important application prospects in clinical treatment.
Description
Technical field
The present invention relates to a kind of albumen for improving Chemotherapy of Cervical Cancer drug susceptibility, specifically a kind of ZNF496 albumen
Application in terms of improving Chemotherapy of Cervical Cancer drug susceptibility, belongs to field of medicaments.
Background technique
Cervical carcinoma (Cervical cancer) is the second common cancer in women, and global female cancer death
The third-largest reason, there are about 500,000 new cases and 250,000 deaths every year.Cervical cancer pathogenesis rate rises year by year, and average year increases
Rate is 0.6%, and morbidity and dead high incidence age are in obvious rejuvenation trend.The generation of cervical carcinoma and microorganism include bacterium, disease
The infection of poison etc. is closely related, and high-risk HPV persistent infection is the Major Risk Factors of cervical carcinoma, 90% or more cervical carcinoma companion
There is high-risk HPV infection.It but is that multistage, a variety of accesses, polymolecular factor are comprehensive to cervical carcinoma is eventually developed to after HPV infection
The result of cooperation.The conventional treatment model of cervical carcinoma is postoperative irradiation, and chemotherapy is used only for cannot performing the operation or the evening of radiotherapy
The palliative treatment of patient is shifted outside phase patient, recurrence and pelvic cavity.Therefore, screen and identify the different of cervical carcinoma occurrence and development each stage
Normal molecular events understand the signals-modulating mechanism of cervical carcinoma occurrence and development in depth, establish the pre-alarming system of its early diagnosis, research and development
Novel tumor-targeting drug has great strategy to the survival rate for improving cervical cancer patient and the life quality for improving patient
Meaning.
Cis-platinum (Cisplatin) can inhibit the DNA replication dna process of cancer cell, and damage structure on its cell membrane, have relatively strong
Broad spectrum anticancer effect, for the first-line drug of a variety of solid tumors for the treatment of cervical carcinoma etc..But with the progress of oncotherapy, cis-platinum
Therapeutic effect can be gradually reduced, and some cervical cancer patients act on it insensitive, or even can be generated chemotherapy resistance, be answered its clinic
With receiving very big restriction.The new type antineoplastic medicine for finding and finding raising cisplatin sensitivity, is cervical carcinoma clinical treatment
In one of critical issue urgently to be resolved.
In on chromosome 1q44, its mRNA overall length is 2453 bp for the ZNF496 assignment of genes gene mapping, and wherein the area CDS is 1764
Bp, 587 amino acid of codified.ZNF496 including mouse, ox, chimpanzee and people etc. have homologous base between multiple species
Cause.ZNF496 protein structure domain is followed successively by the zinc finger of SCAN, KRAB, C2HR and 4 tandem sequence repeats from N-terminal to C-terminal.As other
KRAB type zinc finger protein is the same, the phase interaction between the main mediating protein-protein of the SCAN and KRAB structural domain of ZNF496
With.In addition, C2HR also can be with the transmethylase NSD1(nuclear receptor binding SET domain of H3K36
Protein 1) it combines, play the transcriptional suppression that KAP-1 is not depended on.Nielsen etc. reports that ZNF496 passes through C2HR for the first time
Structural domain interacts with NSD1, and NSD1 is a kind of istone lysine methylferase, with Sotos syndrome, children
Acute myeloblastic leukemia is closely related with giantism.In addition, ZNF496 also with Jarid2(AT rich interactive
Domain 2, jumonji) it interacts, ZNF496 can inhibit the transcriptional suppression of Jarid2, and Jarid2 is in embryo
Fetal hair plays an important role in educating.So far, also seldom to the research of the biological function of ZNF496 and mechanism.
Summary of the invention
The object of the present invention is to provide a kind of ZNF496 albumen in terms of improving Chemotherapy of Cervical Cancer drug susceptibility
Using enhancing cis-platinum to the chemosensitivity of cervical carcinoma, to effectively improve facing for cervical carcinoma by the expression of ZNF496 albumen
Bed curative effect provides new drug targets selection.
The technical solution of the present invention is as follows:
Application of the ZNF496 albumen in terms of improving Chemotherapy of Cervical Cancer drug susceptibility, to increase Chemotherapy of Cervical Cancer drug susceptibility
The solution of problem provides new target spot and therapeutic strategy.
Stable transfection is distinguished using ZNF496 over-express vector and/or transiently transfects cervical cancer cell Hela, treatment with chemotherapy
Drugs Cisplatin processing, increases induction of the cis-platinum to Hela Cell Apoptosis；Stablized by ZNF496 and is overexpressed to increase cis-platinum
To the inhibiting effect of cervical cancer cell proliferation；ZNF496 can effectively enhance the inhibition that cis-platinum grows cervical cancer cell in vivo
Effect.
The invention has the benefit that providing the new influence cervical cancer cell of one kind to the factor of cisplatin sensitivity, it is
The mechanism of action that research ZNF496 influences tumour cell chemotherapy drug susceptibility has established experiment basis.It, can using this mechanism
To design specific targeted therapy scheme, and it is applied to the preparation that ZNF496 is overexpressed preparation medicine, use in conjunction chemotherapeutics,
Accurately individualized treatment is implemented to cervical cancer patient, it is with important application prospects in clinical treatment.
Present invention will be further explained below with reference to the attached drawings and examples.
Detailed description of the invention
Fig. 1 is that Western blot identifies using slow virus over-express vector and accordingly unloaded right in cervical cancer Hela cells
After carrier stable transfection, the ZNF496 screened, which stablizes, is overexpressed cervical cancer cell lines pLV-Neo-ZNF496-1, pLV-
The expression of ZNF496 albumen in Neo-ZNF496-2 and unloaded control stable cell line Con；
Fig. 2 is that cell apoptosis assay detects the stable influence (Fig. 2-A being overexpressed to cisplatin induction Hela Cell Apoptosis of ZNF496
It indicates to stablize using flow cytomery ZNF496 and is overexpressed cervical cancer cell lines pLV-Neo-ZNF496-1, pLV-Neo-
The apoptosis rate that ZNF496-2 and unloaded control stable cell line Con are induced through 10 μM of 24 h of cisplatin treated；Fig. 2-B indicates each group
Between the statistics of apoptosis rate compare；Data compare between two groups is examined using t；* representing experimental group and control group has conspicuousness
(* represents P < 0.05 to difference；* represents P < 0.01))；
Fig. 3 is the expression of ZNF496 albumen after utilizing transient transfection in Western blot identification cervical cancer Hela cells；
Fig. 4 is that cell apoptosis assay detection ZNF496 is instantaneously overexpressed influence (Fig. 4-A to cisplatin induction Hela Cell Apoptosis
It indicates using flow cytomery PCMV-Myc-ZNF496 and corresponding zero load control plasmid Con in cervical cancer Hela cells
After 18 h of instantaneous overexpression, the apoptosis rate through 10 μM of 36 h of cisplatin treated induction；Apoptosis rate between Fig. 4-B expression each group
Statistics compares；Data compare between two groups is examined using t；* represent experimental group and control group have significant difference (* represent P <
0.05；* represents P < 0.01；* * represents P < 0.001))；
Fig. 5 is that plate clone forms the stable influence being overexpressed to the cervical cancer cell proliferation of cisplatin effect of experiment detection ZNF496
(Fig. 5-A indicate plate clone formed experiment detection ZNF496 stablize be overexpressed cervical cancer cell lines pLV-Neo-ZNF496-1 and
Zero load control stable cell line Con is through the cell proliferative conditions after cisplatin treated 2 weeks of 1 μM, 1.5 μM；It is thin between Fig. 5-B expression each group
The statistics that born of the same parents clone number compares；Data compare between two groups is examined using t；* representing experimental group and control group has significant difference
(* represents P < 0.05；* represents P < 0.01；* * represents P < 0.001))；
Fig. 6 is the cervical cancer cell tumor growth that nude mice by subcutaneous tumor formation experiment detection ZNF496 stablizes overexpression to cisplatin effect
Influence (the stable overexpression cervical cancer cell lines pLV-Neo-ZNF496-1 of Fig. 6-A expression ZNF496 and the stable cell of unloaded control
Strain Con is inoculated with nude mice by subcutaneous, the tumour growth situation after cis-platinum (1 mg/kg) is handled 30 days；Fig. 6-B indicates tumour body between each group
Product growth curve；Fig. 6-C indicates the comparison of tumor weight between each group；Data compare between two groups is examined using t；* experimental group is represented
Having significant difference with control group, (* represents P < 0.05；* represents P < 0.01)).
Specific embodiment
Hereinafter, preferred embodiments of the present invention will be described, it should be understood that preferred embodiment described herein is only used
In the description and interpretation present invention, it is not intended to limit the present invention.
Embodiment 1
ZNF496 stablizes the building for being overexpressed cervical cancer cell lines
(1) pass through the CDS overall length of the method human cloning ZNF496 gene of molecular biology；
(2) PCR amplification and clone products are recycled；
(3) recovery product is connected on carrier pLV-Neo, double digestion identification, and be sequenced；
(4) correct through above-mentioned sequencing, the successful plasmid of building carries out slow virus packaging:
A.293T cell inoculation is to 25 cm2Two bottles of culture bottle, when cell it is long to 80% when transfected；
B. in cell superclean bench, two 1.5 clean mL centrifuge tubes are taken, it is each that 1 mL antibiotic-free and serum-free is added
Culture medium.Wherein purpose plasmid pLV-Neo-ZNF496(5 μ g is added in a centrifuge tube) and packaging plasmid psPAX2(3.75
μ g), pMD2.G(1.25 μ g), mix.Purpose plasmid pLV-Neo(5 μ g is added in another centrifuge tube) and packaging plasmid
PsPAX2(3.75 μ g), pMD2.G(1.25 μ g), mix；
C. above-mentioned two centrifuge tubes are respectively added 20 μ L Tranasfection Reagent and mix well, and are incubated at room temperature 20 min
Afterwards, two are added separately to be inoculated in the culture bottle of 293T cell；
D. fluid infusion after 6 h is transfected, cell is carried out changing liquid again after 22 h, continues to collect culture supernatant after cultivating 50 h；1200
Rpm, 3 min, 0.22 μm of filter filtering, are dispensed into EP pipe；
(5) by above-mentioned packaged virus infection HeLa Cells, the culture medium that 96 h are changed to the drug containing G418 is infected
It is screened, until cytotostatic is survived；
(6) stable cell dissociation will be screened as individual cells, infinite dilution continues to cultivate into six orifice plates, to individual cells
Grow up to individual cells group, chooses unicellular group and be put into 24 orifice plates containing fresh culture and cultivate；
(7) a part of cell continues to cultivate, and a part of leach protein carries out the expression quantity of Western blot identification ZNF496, thus
It filters out ZNF496 and stablizes the HeLa cell strain being overexpressed.
According to the method for embodiment 1, it identifies that ZNF496 stablizes by Western blot and is overexpressed efficiency, as a result such as Fig. 1
It is shown.ZNF496 albumen is in stablizing overexpression cervical cancer cell lines pLV-Neo-ZNF496-1, pLV-Neo-ZNF496-2
All more unloaded control stable cell line Con is expressed to obviously increase.This is provided for further progress cervical carcinoma medicaments insensitive Journal of Sex Research
Important tool.
Embodiment 2
Cell apoptosis assay detects influence of the ZNF496 to cervical cancer cell cisplatin medicine sensibility
(1) ZNF496, which is overexpressed, stablizes HeLa cell strain, and cisplatin treated carries out cell apoptosis assay
A. stable HeLa cell strain pLV-Neo-ZNF496-1, pLV-Neo-ZNF496-2 is overexpressed to ZNF496 and its zero load is right
It is digested, 800 rpm, 3 min, is counted according to strain cell is stablized；
B. the ZNF496 of identical quantity is overexpressed stable HeLa cell strain and unloaded compare stablizes six orifice plate of strain cell inoculation；
C. when cell it is long to 70%-80% when agent-feeding treatment, the every hole of experimental group is added 2 mL and contains Cisplatin(10 μM of cis-platinum)
Culture medium, control group is added 2 mL and contains the culture medium of equivalent DMSO, after 24 h, collects cell；
D. culture medium in six orifice plates is directly outwelled, after 1 × PBS of addition washes a cell, digestion.By cell move into 1.5 mL from
In heart pipe, 70 × g, 3 min, 4 DEG C；
E. supernatant is removed, 500 μ 1 × PBS of L are added, (guarantees that the number of each sample piping and druming is the same) under slight piping and druming 3,70 × g,
3 min, 4 DEG C；
F. supernatant is removed, 1 × Binding Buffer of 300 1 × PBS of μ L configuration is respectively added in each sample, while 5 μ L are added
Annexin V/APC and 5 μ L PI are marked, and are protected from light room temperature and dye 15 min, and at interval of 5 min, slight cell of blowing and beating makes
Abundant dyeing；
G. it filters, places on ice, carry out flow cytomery changes of cell apoptosis.
According to the method for embodiment 2(1), pass through the protein stabilized overexpression cervical cancer cell of flow cytomery ZNF496
Apoptosis situation before and after strain and unloaded control cell strain cisplatin treated.As a result as shown in Fig. 2, chemotherapeutic drugs Cisplatin can induce
Hela Cell Apoptosis, and after the protein stabilized overexpression of ZNF496, pLV-Neo-ZNF496-1, pLV-Neo-ZNF496-2 group
The apoptosis rate of cisplatin induction is all apparently higher than control group Con.This, which shows that ZNF496 stablizes to be overexpressed, can increase chemotherapeutic
The Hela Cell Apoptosis rate of object cisplatin induction.
(2) ZNF496 is overexpressed plasmid and transiently transfects HeLa cell, and cisplatin treated carries out cell apoptosis assay
A.HeLa cell is passed on, and 4 holes of six orifice plates are inoculated with, when cell it is long to 70% when transfected, two holes transfections
ZNF496 is overexpressed plasmid PCMV-Myc-ZNF496, and two holes transfect unloaded control plasmid PCMV-Myc, each 2 μ g；It transiently transfects
Cell is received after 18 h and carries out Western blot, identifies the expression quantity of ZNF496；
When b. carrying out Antibiotics resistance test, after 18 h of plasmid transfection, two holes of experimental group change 2 mL and contain cis-platinum Cisplatin
The culture medium of (10 μM), control group change the culture medium that 2 mL contain equivalent DMSO, are handled；
C.36 after h, culture medium in six orifice plates is directly outwelled, after 1 × PBS of addition washes a cell, digestion.Cell is moved into
In 1.5 mL centrifuge tubes, 70 × g, 3 min, 4 DEG C；
D. supernatant is removed, 500 μ 1 × PBS of L are added, (guarantees that the number of each sample piping and druming is the same) under slight piping and druming 3,70 × g,
3 min, 4 DEG C；
E. supernatant is removed, 1 × Binding Buffer of 300 1 × PBS of μ L configuration is respectively added in each sample, while 5 μ L are added
Annexin V/APC and 5 μ L PI are marked, and are protected from light room temperature and dye 15 min, and at interval of 5 min, slight cell of blowing and beating makes
Abundant dyeing；
F. it filters, places on ice, carry out flow cytomery changes of cell apoptosis.
According to the method for embodiment 2(2) a, it is thin to identify that ZNF496 transiently transfects cervical carcinoma by Western blot first
The overexpression efficiency of born of the same parents, as a result such as Fig. 3 is shown, compared with the unloaded control plasmid of transfection, ZNF496 is overexpressed plasmid and instantaneously turns
After dye, ZNF496 protein expression is significantly improved in cervical cancer cell.Then according to the method for embodiment 2(2) bcdef, pass through stream
Formula cell instrument detection ZNF496 albumen is instantaneously overexpressed cell before and after cervical cancer cell lines and unloaded control cell strain cisplatin treated
Apoptosis situation.As a result as Fig. 4 shows that ZNF496, which is instantaneously overexpressed, can induce Hela Cell Apoptosis, and ZNF496 is instantaneous
After cisplatin treated, apoptosis rate obviously increases than the apoptosis induction rate of unloaded control cell the cell of overexpression.The result into
One step, which demonstrates ZNF496 albumen, can increase the cervical cancer cell sensibility apoptosis-induced to chemotherapeutic drugs Cisplatin.
Embodiment 3
Plate clone forms influence of the experiment detection ZNF496 to cervical cancer cell cisplatin medicine sensibility
(1) by identical quantity (1 × 103) stablizing for ZNF496 be overexpressed HeLa cell strain pLV-Neo-ZNF496-1 and zero load
Control cell strain is inoculated into six orifice plates；Every three holes are multiple holes；
(2) exchanged fresh culture for every three days, experimental group is changed containing Cisplatin(1 μM of cis-platinum, 1.5 μM) fresh training
Base processing is supported, control group changes the fresh culture processing of equivalent DMSO；
After (3) 2 weeks, observation receives plate if number of cell clones can count and be unlikely to excessive；
(4) culture medium directly is removed, blots net residual liquid with pipettor；1 mL is carefully added into containing 0.1% knot along side in six orifice plates
The methanol solution of crystalviolet, is dyed, and 20 min are dyed；
(5) dyeing liquor is carefully outwelled, six orifice plates is slowly cleaned with tap water, be careful not to clone and wash out；
(6) it after drying, takes pictures, it is for statistical analysis.
According to the method for embodiment 3, experiment detection ZNF496 is formed by plate clone and stablizes overexpression to cisplatin effect
Cervical cancer cell proliferation influence, as a result show such as Fig. 5.ZNF496 stablizes the clone for being overexpressed and being able to suppress cervical cancer cell
It is formed；It is and right after the cisplatin treated of various concentration can inhibit the Clone formation of cervical cancer cell, and ZNF496 is overexpressed
It is compared according to a group Con, clone formation number significantly reduces, this shows that ZNF496 stablizes to be overexpressed and increases cis-platinum to cervical cancer cell
Inhibited proliferation.
Embodiment 4
ZNF496 influences cervical carcinoma to the In vivo study of cisplatin medicine sensibility
(1) Female nude mice of selection 4-5 week old, every group 5, with 2 × 106/ quantity only, be inoculated with respectively ZNF496 be overexpressed it is steady
Determine cervical cancer cell lines pLV-Neo-ZNF496-1 and unloaded control cell strain；
(2) cis-platinum experimental group takes the mode of intraperitoneal administration every three days after being inoculated with, and gives cis-platinum Cisplatin(1 mg/kg)；
Control group gives PBS；
(3) every the three days major diameters and minor axis with vernier caliper measurement tumour, and with balance measurement nude mice weight；
(4) it after being inoculated with 30 days, takes off neck and puts to death nude mice, remove knurl.Measure the length, width and height of tumour and the weight of tumour；
(5) tumor growth curve in nude mouse is drawn.
According to the method for embodiment 4, detection ZNF496 is tested by nude mice by subcutaneous tumor formation and stablizes overexpression to cisplatin effect
Cervical cancer cell tumor growth influence, as a result as shown in Figure 6.ZNF496, which stablizes to be overexpressed, is able to suppress cervical cancer cell
Internal one-tenth knurl ability and tumorous size；After cisplatin treated, it is suppressed that cervical cancer cell is in the intracorporal one-tenth knurl ability of nude mice and knurl
Size, and ZNF496 be overexpressed after, compared with control group Con, cervical cancer cell is obvious in the intracorporal one-tenth knurl ability of nude mice
It reduces, tumorous size is also obviously reduced.This shows that ZNF496 overexpression significantly improves cis-platinum to cervical cancer cell tumor growth
Inhibiting effect, increase cervical cancer cell to the sensibility of chemotherapeutic drugs Cisplatin.
Claims (6)
1.ZNF496 application of the albumen in terms of improving Chemotherapy of Cervical Cancer drug susceptibility.
2. application of the ZNF496 albumen according to claim 1 in terms of improving Chemotherapy of Cervical Cancer drug susceptibility, special
Sign is: using ZNF496 over-express vector difference stable transfection and/or transiently transfecting cervical cancer cell lines, treatment with chemotherapy drug
Cisplatin treated increases induction of the cis-platinum to Hela Cell Apoptosis；Stablized by ZNF496 and is overexpressed to increase cis-platinum to uterine neck
The inhibiting effect of cancer cell multiplication.
3. application of the ZNF496 albumen according to claim 1 in terms of improving Chemotherapy of Cervical Cancer drug susceptibility, special
Sign is: being stablized by ZNF496 and is overexpressed to increase chemotherapeutic drugs Cisplatin to the inducing action of cervical cancer cell Hela apoptosis.
4. application of the ZNF496 albumen according to claim 1 in terms of improving Chemotherapy of Cervical Cancer drug susceptibility, special
Sign is: being instantaneously overexpressed by ZNF496 to induce Hela Cell Apoptosis, and it is thin to cervical carcinoma to increase chemotherapeutic drugs Cisplatin
The inducing action of born of the same parents' apoptosis.
5. application of the ZNF496 albumen according to claim 1 in terms of improving Chemotherapy of Cervical Cancer drug susceptibility, special
Sign is: stablizing the internal one-tenth knurl ability and tumorous size that are overexpressed to inhibit cervical cancer cell by ZNF496.
6. application of the ZNF496 albumen according to claim 1 in terms of improving Chemotherapy of Cervical Cancer drug susceptibility, special
Sign is: by cisplatin treated, to inhibit the size of cervical cancer cell one-tenth knurl ability in vivo and knurl, crossing table in ZNF496
After reaching, inhibiting effect is more obvious.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101375860A (en) * | 2008-09-18 | 2009-03-04 | 武汉大学 | Application of cisplatin combined with hTERT-HRP/IAA in medicament for treating cervical cancer cell |
| CN107540736A (en) * | 2016-06-23 | 2018-01-05 | 首都医科大学 | To cervical carcinoma along the related large biological molecule NHERF1 of the property of medicine and its application |
-
2019
- 2019-07-03 CN CN201910591721.7A patent/CN110151976B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101375860A (en) * | 2008-09-18 | 2009-03-04 | 武汉大学 | Application of cisplatin combined with hTERT-HRP/IAA in medicament for treating cervical cancer cell |
| CN107540736A (en) * | 2016-06-23 | 2018-01-05 | 首都医科大学 | To cervical carcinoma along the related large biological molecule NHERF1 of the property of medicine and its application |
Non-Patent Citations (4)
| Title |
|---|
| TAO TAO等: "NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells", 《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》 * |
| YAO YANG等: "Up-regulation of microRNA-664 inhibits cell growth and increases cisplatin sensitivity in cervical cancer", 《INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE》 * |
| 王进龙: "ZNF496在乳腺癌发生发展中功能与作用机制的研究", 《中国优秀硕士学位论文全文数据库 医药卫生科学辑》 * |
| 魏茜雪等: "宫颈癌组织和Hela细胞中miR-664的表达及其对顺铂化疗敏感性的影响", 《江苏大学学报（医学版）》 * |
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