Molecular changes to HeLa cells on continuous exposure to cisplatin or paclitaxel
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
References
Differentiation of human colon cancer cells changes the expression of beta-tubulin isotypes and MAPs
Different mechanisms for gamma-glutamyltransferase-dependent resistance to carboplatin and cisplatin
Citations
Factors affecting sensitivity to antitumor platinum derivatives of human colorectal tumor cell lines
Effects of propolis extract on sensitivity to chemotherapeutic agents in HeLa and resistant sublines
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