Study of therapy resistance in cancer cells with functional proteome analysis

Study of therapy resistance in cancer cells with functional proteome analysis
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DOI:
10.1515/cclm.2002.037
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发表时间:
2002-01-01
影响因子:
6.8
通讯作者:
Sinha, P
Sinha, P
中科院分区:
医学2区
文献类型:
--
作者:
Poland, J;Schadendorf, D;Sinha, P

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Different types of cancer are naturally resistant to many anticancer drugs. Additionally, these tumours develop acquired drug resistance, which includes the classical multidrug resistance (MDR) accompanied by the synthesis of Pglycoprotein, a member of the superfamily of ATPbinding cassette (ABC) transporters. Furthermore, atypical MDR is mediated by several different, some unkown, mechanisms. To overcome chemoresistance problems, antineoplastic drugs are often combined with other modes of therapy, e.g. hyperthermia where good response has been reported in several experimental tumour models and in advanced cancer patients. The success of this combined anticancer treatment may be limited by an increase in chemoresistance and thermoresistance.A model system to study resistance phenomena is the use of chemoresistant and thermoresistant cancer cell lines. We have established chemoresistant cancer cell lines (gastric and pancreatic carcinoma, fibrosarcoma, melanoma) and now thermoresistant cell lines derived from gastric and pancreatic carcinoma cells and their counterparts that were resistant towards daunorubicin (classical MDR) and mitoxantrone (atypical MDR).Using proteomics, in this paper we evaluate the drug resistance of chemoresistant melanoma cells (parental cell line MeWo and sublines exhibiting drug resistance towards etoposide, cisplatin, fotemustine and vindesine) as a paradigm for analysis of drug resistance phenomena. Additionally, we investigate heat resistance and the interaction of chemoresistance and thermoresistance to identify common pathways using the parental and drug resistant stomach cancer cell lines EPG85-257, EPG85-257RNOV, EPG85- 257RDB and their thermoresistant counterparts. Possible implications of differential protein expression will be discussed.