In vitro cytotoxity and reversal effects of PHⅡ-7 in human multidrug-resistant breast cancer MCF-7/ ADR cells
- VernacularTitle:PHⅡ-7对人乳腺癌多药耐药细胞MCF-7/ADR体外杀伤活性和逆转耐药作用
- Author:
Ruizan SHI
;
Xiuli ZHANG
;
Ming YANG
;
Yanjun ZHANG
;
Hongwei PENG
;
Simei REN
;
Yang LIN
;
Rong LIU
;
Wei LI
;
Dongsheng XIONG
- Publication Type:Journal Article
- Keywords:
PHⅡ-7;
multidrug resistance;
mdr1;
P-gp;
reverse resistance
- From:
China Oncology
2001;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
Background and purpose:Multidrug resistance(MDR)is one of the major causes of progressive breast cancer chemotherapy failure.One of the major mechanisms of MDR is the overexpression of P-glycoprotein (P-gp).Therefore,the identification of novel agents which can inhibit the drug transporter function of P-gp or its expression is of utmost interest in cancer research.The aim of this study was to explore the antitumor and reversal effect of PHⅡ-7,natural products from traditional Chinese medicine(TCM).Methods:The cytotoxicity of PHⅡ7 alone and combined application of PHⅡ-7 and adriamycin(ADR)on breast cancer cells were determined using MTT assay.Annexin V–FITC/PI apoptosis detection kit was used to observe the apoptosis-inducing effect of PHⅡ-7 in MCF-7 and MCF-7/ADR cells.The effect of PHⅡ-7 on mdr1 mRNA was determined by reverse transcription PCR and real time PCR,flow cytometer was used to measure the intracellular ADR accumulation.Results:PHⅡ-7 alone inhibited cell growth of MCF-7 and MCF-7/ADR cells with the IC 50 (6.07?0.85),(5.51?1.22)?mol/L,respectively when combined with ADR,PHⅡ-7 enhanced the cytotoxicity of ADR toward MCF-7/ADR cells.In addition,PHⅡ-7 induced apoptosis both on MCF-7 and MCF-7/ADR cells;PHⅡ-7 reversed the drug resistance to ADR in MCF-7/ADR cells by inhibiting mdr1 mRNA transcription and increasing the intracellular ADR accumulation.Conclusion:PHⅡ-7 displayed significant anti-proliferative and apoptosis-inducing effect on sensitive and multidrug resistant breast cells in vitro.PHⅡ-7 reversed effectively MDR by blocking the drugs to be pumped out by inhibiting P-gp expression and function pathway.
