4.5 Article

ABCG2 regulates the pattern of self-renewing divisions in cisplatin-resistant non-small cell lung cancer cell lines

Journal

ONCOLOGY REPORTS
Volume 32, Issue 5, Pages 2168-2174

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3470

Keywords

ABCG2; drug resistance; NSCLC; symmetric division; asymmetric division

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Funding

  1. National Natural Science Foundation of China [81201684]

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Overexpression of ABCG2 is considered a major mechanism of cancer drug resistance. Recent studies have shown that ABCG2 can regulate the switch between symmetric and asymmetric cell division in adult stem cells; however, the relationship between ABCG2 and cell division in drug-resistant cancer cells remains to be determined. In the present study, we demonstrated that ABCG2 is involved in the cell division of drug-resistant cancer cells. We first established drug-resistant H460 and A549 cell lines by repeated exposure to cisplatin and found that the expression of ABCG2 in these cell lines was significantly increased. As evidenced by PKH-26 staining, these drug-resistant cell lines favored symmetric division, which differed from the asymmetric division of the parental cells. Furthermore, we established stable ABCG2-overexpressing and stable shRNA-ABCG2-knock-down cell lines to evaluate the potential role of ABCG2 in cancer cell division. The results showed that overexpression of ABCG2 in A549 parental cells significantly increased the proportion of symmetric division, whereas knockdown of ABCG2 in drug-resistant A549 cells significantly increased the proportion of asymmetric division. Taken together, our findings suggest that ABCG2 is involved in the modulation of cancer drug resistance by regulating the pattern of cell division. The present study provides novel insight into the role of ABCG2 in cancer treatment resistance.

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