The COX-2 inhibitor Celecoxib enhances the sensitivity of KB/VCR oral cancer cell lines to Vincristine by down-regulating P-glycoprotein expression and function

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• 作者：Yi Xuan Yan^a ; ^b ; ^{yanyixuan001@163.com} ; Wei Zhong Li^a ; ^b ; ^{liwz@fimmu.com} ; ^{gzliwz@126.com} ; Yan Qing Huang^a ; ^b ; ^{sdzchyq@163.com} ; Wen Xiao Liao^a ; ^b ; ^{liaowenxiao2011@163.com}
• 关键词：Cyclooxygenase 2 ; Celecoxib ; Multidrug resistant ; P-glycoprotein ; KB/VCR cell
• 刊名：Prostaglandins and Other Lipid Mediators
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：97
• 期：1-2
• 页码：29-35
• 全文大小：657 K

文摘

Previous studies have indicated that long-term chemotherapy decreases the sensitivity of oral cancer cells to chemotherapeutics while simultaneously increasing resistance to these drugs. COX-2 inhibitors are known to enhance the toxic action of anti-tumor drugs against cancer cells. Using the MTT method, we investigated the influence of the COX-2 selective inhibitor Celecoxib on the proliferation of KB/VCR oral cancer cell lines and analyzed the effect of Celecoxib on the regulation of P-glycoprotein (P-gp) expression and function. Western blot analysis was employed to detect the expression of P-gp, and flow cytometry was used to evaluate P-gp function by detecting the accumulation of the active P-gp functional fluorescence substrate within KB/VCR cells. The results revealed that a low dose of Celecoxib (10 ¦Ìmol/L) showed no growth inhibitory effects on KB/VCR cell lines. When the concentration of Celecoxib was greater than or equal to 20 ¦Ìmol/L, the inhibitory effect on KB/VCR cells was significantly enhanced in a time- and dose-dependent manner. The lower dose of Celecoxib (10 ¦Ìmol/L) significantly enhanced the toxicity of Vincristine (VCR) against KB/VCR cell lines. After the application of Celecoxib plus VCR (10 ¦Ìmol/L + 1.5 ¦Ìmol/L, respectively) treatment for 24, 48 or 72 h, the growth inhibition rates of KB/KBV cells were 37.82 ¡À 1.60 % , 47.84 ¡À 1.29 % and 54.43 ¡À 2.35 % , respectively, which were significantly higher than the rates in the cells treated only with Celecoxib (10 ¦Ìmol/L) or VCR (1.5 ¦Ìmol/L) (all P < 0.01). P-gp expression levels in KB/KBV cells treated with Celecoxib plus VCR (10 ¦Ìmol/L + 1.5 ¦Ìmol/L, respectively) were markedly lower than the levels in control cells and those treated with VCR (1.5 ¦Ìmol/L) (all P < 0.01). In addition, the intensity of Rho123 fluorescence of KB/KBV cells in cells treated with Celecoxib plus VCR (10 ¦Ìmol/L + 1.5 ¦Ìmol/L, respectively) or Celecoxib alone (10 ¦Ìmol/L) was significantly higher than the intensity observed in control cells and those treated with VCR alone (1.5 ¦Ìmol/L) (all P < 0.01). The underlying mechanism of these phenomena is likely correlated with the down-regulation of the expression and function of P-gp due to Celecoxib, thereby increasing the amount of VCR accumulated in KB/VCR cells.