Cisplatin is one of the most commonly used drugs in the treatment of gastric cancer. However,
drug resistance is a major obstacle for effective treatment and originates in multiple mechanisms such as
enhanced DNA repair and anti-apoptosis. Our previous results demonstrated that XRCC1 was a key
regulator of cisplatin induced DNA damage and apoptosis. TXNL1, a member of the thioredoxin family, negatively
regulated the expression of XRCC1 via the ubiquitin-proteasome pathway. Here, we investigated the role of TXNL1 in
the apoptosis induced by cisplatin. Our data showed that the expression of TXNL1 in the cisplatin resistant gastric cancer
cell lines BGC823/DDP and SGC7901/DDP cells was significantly lower compared with the cisplatin sensitive cell lines
BGC823 and SGC7901. Inhibition of the expression of TXNL1 in BGC823 and SGC7901 cells led to increased resistance to
cisplatin induced apoptosis and cell death detected by Tunel and clonogenic assay, respectively. In contrast, over expression
of TXNL1 in BGC823/DDP and SGC7901/DDP cells lead to higher cisplatin induced apoptosis and cell death. Moreover,
our results demonstrated that the mechanism of TXNL1 regulating cisplatin-induced apoptosis was closely associated
with Bcl-2 mediated mitochondria apoptosis pathway. In conclusion, these findings suggest that TXNL1 was a feasible
modulator and potential chemotherapeutic target for the cisplatin resistant phenotype of human gastric cancer cells.
Keywords: Apoptosis, Bcl-2, cisplatin, gastric cancer, TXNL1, XRCC1.
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