Differential sensitivity to paclitaxel-induced apoptosis and growth suppression in paclitaxel-resistant cell lines established from HEC-1 human endometrial adenocarcinoma cells

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To investigate acquired paclitaxel (PTX) resistance in cancer cells, we established five monoclonal PTX-resistant cell lines from HEC-1 human endometrial adenocarcinoma cells by means of long-term PTX-exposed cultures and limiting dilution cultures. The established PTX-resistant subclones showed apparent resistance to PTX-induced DNA fragmentation but not to PTX-induced growth suppression. None of the five PTX-resistant subclones showed apparent resistance to other anticancer drugs such as cisplatin, etoposide, 5-fluorouracil, pirarubicin-HCl, 4-hydroxy-cyclophosphamide or mitomycin C. Semiquantitative flow cytometric analysis revealed no apparent differential expression of 17 molecules that were previously reported to regulate apoptosis or drug resistance, between the five PTX-resistant subclones and the parent cells. Karyotyping analysis revealed common changes in chromosomes 4 and 18 in the five PTX-resistant subclones but not in the HEC-1 parent cells. These results indicate that PTX-induced growth suppression is regulated by different mechanisms from those involved in PTX-induced apoptosis. It was concluded that these established PTX-resistant subclones can be useful models in studies related to the prevention or treatment of recurrent cancers after PTX chemotherapy.

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