Establishment of an expression platform of OATP1B1 388GG and 521CC genetic polymorphism and the therapeutic effect of tamoxifen in MCF-7 cells

Pu,Zhichen; Zhang,Xuefeng; Chen,Qun; Yuan,Xiaolong; Xie,Haitang

doi:10.3892/or.2015.3864

Establishment of an expression platform of OATP1B1 388GG and 521CC genetic polymorphism and the therapeutic effect of tamoxifen in MCF-7 cells

Authors:
- Zhichen Pu
- Xuefeng Zhang
- Qun Chen
- Xiaolong Yuan
- Haitang Xie
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Affiliations: Department of Clinical Pharmacy, Yijishan Hospital of Wannan Medical College, Anhui Province Center for Drug Clinical Evaluation, Wuhu, Anhui 241001, P.R. China, Department of Pharmacy, Wuhu Chinese Medicine Hospital, Wuhu, Anhui 241001, P.R. China
Published online on: March 18, 2015 https://doi.org/10.3892/or.2015.3864
Pages: 2420-2428

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Abstract

The present study was designed to evaluate the gene polymorphisms of organic anion transporting polypeptide 1B1 (OATP1B1) in predicting the therapeutic efficacy of tamoxifen (TAM) for MCF-7. Established plasmids OATP1Bl wild‑type 388GG and 521CC were transfected into MCF-7 cells and used to determine whether the gene polymorphisms affected the therapeutic efficacy of TAM for MCF-7. The established plasmids pcDNA3.1(‑)-OATP1B1 wild‑type 388GG and 521CC were digested by restriction enzymes and analyzed by gene sequencing. The gene polymorphisms of OATP1Bl in MCF-7 breast cancer cells were examined by RT-PCR and western blot analysis. The results showed that the mutations of OATP1B1 388GG and 521CC led to a decrease of the inhibition and apoptotic rates of MCF-7 cells, albeit not significantly compared to the OATP1B1 group. The G0/G1 phase length ratio was reduced, and the S and G2M phases were increased in the OATP1B1 388GG and 521CC groups, although not significantly compared to the OATP1B1 group. The mutations of OATP1B1 388GG and 521CC inhibited the activity of OATP1B1 protein, restrained the turnover capacity of OATP1B1 and reduced the entrance of TAM into MCF-7 cells, resulting in weakened efficacy of TAM in the treatment of breast cancer.

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