Glutathione conjugation
and transportation of glutathione conjugates of anti
cancer drugs out of
cells are important for detoxification of many anti
cancer drugs. Inhibition of this detoxification system has recently been proposed as a strategy to treat drug-resistant solid tumors.
Gallbladder carcinoma is resistant to many anti
cancer drugs, therefore, it is needed to develop a novel strategy for
cancer therapy. In the present study, we tested the effect of emodin (1,3,8-trihydroxy-6-methylanthraquinone), a reactive oxygen species (ROS) generator reported by our group previously, in combination with cisplatin (CDDP), carboplatin (CBP) or oxaliplatin in treating the
gallbladder carcinoma cell line SGC996. Our results showed that co-treatment with emodin could remarkably enhance chemosensitivity of SGC996
cells in comparison with cisplatin, carboplatin or oxaliplatin treatment alone. We found that the mechanisms may be attributed to reduction of glutathione level,
and downregulation of multidrug resistance-related protein 1 (MRP1) expression in SGC996
cells. The experiments on tumor-bearing mice showed that emodin/cisplatin co-treatment inhibited the tumor growth in vivo via increasing tumor cell
apoptosis and downregulating MRP1 expression.
In conclusion, emodin can work as an adjunct to enhance the anticancer effect of platinum drugs in gallbladder cancer cells via ROS-related mechanisms.