Combination of valproic acid and cisplatin greatly increased the expression of P21 in esophageal cancer cells

Abstract

Introduction: Esophageal carcinoma is among the top 5 common cancers in Iran, and<br><br>despite advances in cancer therapy, the mortality rate of this malignancy still remains<br><br>high. Valproic acid (VPA) is a small molecule with anticancer activities, and cisplatin is<br><br>a chemotherapeutic agent routinely used for esophageal cancer treatment. As current<br><br>knowledge about synergic effects of VPA on cisplatin toxicity is limited, we aimed to<br><br>investigate combinatorial effects of VPA and cisplatin on the expression of P21 and<br><br>P53 in esophageal cancer cells.<br><br>Methods: In present study, KYSE30 cells, which are esophageal carcinoma cells, were<br><br>treated with (1) 1 μg/ml cisplatin and (2) 5 mM VPA + 1 μg/ml cisplatin for 72h. Then,<br><br>the total cellular RNA was extracted and cDNAs were synthesized. For real time RTPCR,<br><br>SYBR green master mix was used and normalized values were plotted as relative<br><br>fold change over untreated cells.<br><br>Results: Real time RT-PCR results revealed that combination of non-toxic VPA and<br><br>cisplatin significantly increased the expression of P21 in KYSE30 cells. To note, the<br><br>expression of P21 in cells only treated with 1 μg/ml cisplatin was calculated as<br><br>5.56±1.05, while cocultur of cells with 5 mM VPA + 1 μg/ml cisplatin enhanced P21<br><br>expression up to 16.33±2.3. Despite its effect on P21 expression, VPA did not induce<br><br>significant changes on P53 expression. In conclusion, present results revealed that VPA<br><br>significantly increased the expression of P21 in cells treated with combination of<br><br>VPA+cisplatin. In agreement with these results, our previous finding indicated that nontoxic<br><br>VPA increased the apoptosis induced by cisplatin in KYSE30 cells. Therefore, it<br><br>could be concluded that VPA affects cisplatin toxicity by inducing P21-dependednt<br><br>apoptosis.