Molecular changes to HeLa cells on continuous exposure to cisplatin or paclitaxel

Cancer Chemotherapy and Pharmacology
Kohji TakaraTeruyoshi Yokoyama

Abstract

To achieve a reversal of multidrug resistance (MDR) in cancer chemotherapy, it is crucial to clarify the characteristics of MDR cells generated by various types of chemotherapeutic agents and to find novel targets. Cisplatin- and paclitaxel-resistant HeLa sublines (HeLa/CDDP and HeLa/TXL, respectively) were established by continuous exposure and their cellular changes were examined based on growth inhibition assays, the transport activity of P-glycoprotein/MDR1, and a RT-PCR analysis of MDR-related factors. HeLa/CDDP cells showed cross-resistance to platinum derivatives, whereas HeLa/TXL cells were resistant to a variety of MDR1 substrates. Transport activity of MDR1 was reduced in HeLa/CDDP cells and the expression of MDR1 was significantly accelerated in HeLa/TXL cells, compared with HeLa cells. In addition, the expression levels of MDR-related transporters (MRP1-5 or BCRP), betatubulin which is a target for taxanes, and apoptosis-regulated factors were comparable among the three cell lines. On the other hand, the mRNA levels of gamma-glutamyl transferase, but not gamma-glutamyl cysteine synthetase, were higher in HeLa/CDDP cells than in HeLa and HeLa/TXL cells. HeLa/CDDP cells showed decreased activity and expression of MDR1...Continue Reading

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Citations

Nov 22, 2007·Cancer Chemotherapy and Pharmacology·Noriaki KitadaTeruyoshi Yokoyama
Jul 21, 2011·Se pu = Chinese journal of chromatography·Xiaofei HanHongbin Xiao
Jan 29, 2011·Journal of Pharmaceutical Sciences·Sayo HoribeMikihisa Takano
Dec 14, 2011·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Kohji TakaraKatsuhiko Okumura
Sep 20, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Martina CeckovaFrantisek Staud
May 9, 2007·Phytotherapy Research : PTR·Kohji TakaraTeruyoshi Yokoyama
Feb 2, 2010·Journal of Microencapsulation·Shigehiko TakegamiTatsuya Kitade
Oct 1, 2011·Biomacromolecules·Jing HuJian R Lu

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