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Cancers 2015, 7(2), 1052-1071;

Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
Author to whom correspondence should be addressed.
Academic Editor: Vita Golubovskaya
Received: 1 April 2015 / Accepted: 3 June 2015 / Published: 16 June 2015
(This article belongs to the Special Issue Cancer Cell Proliferation)
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A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug. View Full-Text
Keywords: RNA silencing; synthetic lethality; taxol; taxol-sensitizer loci RNA silencing; synthetic lethality; taxol; taxol-sensitizer loci

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Huang, S.-L.; Chao, C.C.-K. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects. Cancers 2015, 7, 1052-1071.

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