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

Keywords