Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs

International Journal of Cancer. Journal International Du Cancer
Yizheng LiangM Clynes

Abstract

The human lung carcinoma cell line DLKP was exposed to sequential pulses of 10 commonly used chemotherapeutic drugs (VP-16, vincristine, taxotere, mitoxantrone, 5-fluorouracil, methotrexate, CCNU, BCNU, cisplatin and chlorambucil); resulting cell lines exhibited resistance to the selecting agents (ranging approx. 1.5- to 36-fold) and, in some cases, cross-resistance to methotrexate (approx. 1.4- to 22-fold), vincristine (1.6- to 262-fold), doxorubicin (Adriamycin, approx. 1.1- to 33-fold) and taxotere (approx. 1.1- to 36-fold). Several of the variants displayed collateral sensitivity to cisplatin. A marked increase in in vitro invasiveness and motility was observed with variants pulsed with mitoxantrone, 5-fluorouracil, methotrexate, BCNU, cisplatin and chlorambucil. There was no significant change in invasiveness of cells pulsed with VP-16, vincristine, taxotere or CCNU. All of the pulse-selected variants showed elevated levels of MDR-1/P-gp protein by Western blot analysis, although mdr-1 mRNA levels were not increased (except for DLKP-taxotere). In DLKP-taxotere, MRP1 protein levels were also greatly elevated, but mrp1 mRNA levels remained unchanged. BCRP was upregulated in DLKP-mitoxantrone at both the mRNA and protein leve...Continue Reading

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Citations

Jan 28, 2012·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Ye RenJiang Wang
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Jan 5, 2019·Journal of breast cancer·Chang-Chang Han, Fu-Sheng Wan

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