Verteporfin enhances the sensitivity of LOVO/TAX cells to taxol via YAP inhibition.

Abstract

Studies have reported that taxol (TAX) is an effective drug for the treatment of colorectal cancer; however, its application inevitably results in drug resistance. Overexpression of Yes-associated protein (YAP) is considered one of the factors that cause TAX resistance, which may be inhibited by verteporfin (VP) treatment. The present study aimed to confirm the role of YAP in TAX resistance and to investigate whether the drug sensitivity of the TAX-resistant LOVO/TAX cell line to TAX is affected by VP treatment. The role of YAP in TAX resistance was first determined through vector-mediated overexpression and inhibition of YAP in cells. Reverse-transcription quantitative polymerase chain reaction and western blot analysis were performed for detection of associated mRNA and protein, respectively. An MTT assay was used to detect the drug sensitivity of cells to TAX. The results suggested that compared with that in the native LOVO cell line, YAP expression was significantly increased in LOVO/TAX cells. YAP gene silencing markedly enhanced the drug sensitivity of LOVO/TAX cells to TAX and, on the contrary, the drug sensitivity notably declined when YAP was overexpressed in LOVO cells. The results indicated that YAP gene expression and TAX resistance were correlated. VP treatment suppressed YAP expression and increased the drug sensitivity of LOVO/TAX cells to TAX in a dose-dependent manner. In addition, compared with VP alone, VP and TAX combination therapy had a greater inhibitory effect on YAP expression. VP treatment enhanced the drug sensitivity of LOVO/TAX cells to TAX through inhibiting YAP expression.