Sufentanil attenuates oxaliplatin cytotoxicity via inhibiting connexin 43‑composed gap junction function

Comprehensive strategies for the treatment of colorectal cancer (CRC) have become increasingly important. One of the most important factors is pain relief. Therefore, patients with CRC are concurrently treated with analgesics and chemotherapeutic agents; however, the effects of analgesics on the therapeutic activity of chemotherapeutic agents remain largely unknown. The present study investigated the effects of three widely used analgesics in clinics: Fentanyl, remifentanil and sufentanil, on the cytotoxicity of oxaliplatin, a commonly used chemotherapeutic agent for CRC. Furthermore, the underlying mechanisms of those effects in association with connexin 43 (Cx43)‑composed gap junction (GJ) function were analyzed. The Lovo, Colo320, HCT116 and HT29 human CRC cell lines, with or without Cx43 expression, were used to examine the effects of the three analgesics on the cytotoxicity of oxaliplatin. The results demonstrated that in the cell lines expressing Cx43 (Lovo and Colo320), the cytotoxicity of oxaliplatin was attenuated and Cx43 GJ function was inhibited. Sufentanil, not fentanyl or remifentanil, inhibited Cx43 GJ function effectively, and reduced the cytotoxicity of oxaliplatin. In contrast, these effects were not observed in the other two colon cancer cell lines not expressing Cx43 (HCT116 and HT29). These results suggested that alternation of Cx43 GJ function may regulate the cytotoxicity of oxaliplatin in regard to CRC. Furthermore, sufentanil, not fentanyl or remifentanil, suppressed the cytotoxicity of oxaliplatin through inhibition of Cx43 GJ function. These results may be beneficial for the treatment of CRC and reduction of treatment resistance.