Purpose: Taxol is an effective chemotherapeutic agent against epithelial-derived carcinomas, and resistance of carcinoma cells to taxol has developed with the wide prescription of the drug. In this study, five different epithelial carcinoma cell lines were randomly employed to screen the resistant cell line to taxol, and to explore the probable mechanism of taxol-resistant development.
Materials and methods: Cells were grouped into the controls and the taxol treated. The treatment effects of five different epithelial carcinoma cell lines, including CNE1, Hep3B-2, MGC, MCF-7, and NCI-H1299, after being treated by taxol were analyzed through inspecting the ratios of cellular apoptosis, inhibition of cellular proliferation, the capability of cell colony formation and wound recovery, and the interference of cell motility and invasion, while western blot analysis and siRNA targeting Op18/stathmin were applied to explore the probable mechanism on the taxol resistance difference in these cells.
Results: Nonsmall cell lung cancer NCI-H1299 cells presented obvious taxol resistance, and the inhibition of cell motility and invasion was also the weakest in taxol-treated NCI-H1299 cells among these five cell lines. Microtubule dynamics analysis demonstrated that taxol treatment destroyed normal microtubule arrays and caused obvious microtubule collapse in CNE1, Hep3B-2, MGC, and MCF-7 rather than NCI-H1299, while the latter expressed high levels of microtubule-destabilizing protein Op18/stathmin. Inhibition of Op18/stathmin expression increased the sensitivity to taxol and promoted cellular apoptosis in NCI-H1299 cells.
Conclusion: NCI-H1299 cells are evidently resistant to taxol-induced cellular apoptosis, inhibition of cellular proliferation and wound recovery, as well as cell migration and invasion interference, which are closely associated with the changes of microtubule dynamics. High expression of Op18/stathmin is perhaps a crucial determinant of taxol-resistant development in NCI-H1299 cells.
Keywords: Op18/stathmin; epithelial carcinoma cells; microtubule; nonsmall cell lung cancer; taxol resistance.