Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts

Abstract

Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carcinoma CNE-2 cells and whether morphine affects the antitumor activity of cisplatin on tumor growth in human nasopharyngeal carcinoma CNE-2 xenografts in nude mice. We showed that a pretreatment with morphine (1 μg/ml) inhibited the sensitivity of CNE-2 cells to cisplatin by inhibiting cisplatin-induced CNE-2 cell apoptosis, decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. However, a high dose of morphine (1000 μg/ml) had the opposite effect. We also showed that at a low dose, morphine enhances chemoresistance in an in vivo nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models in vitro and in vivo by inhibiting cisplatin-induced apoptosis and decreasing neovascularization.

Morphine contributed to the deterioration of cancer via miR-543/MARCKS/FcγR-mediated phagocytosis pathway

“…Bimonte et al discovered that morphine accelerated angiogenesis and breast cancer development at clinical appropriate doses. And low dose of morphine can suppress the sensitivity to cisplatin in CNE‐2 cells by inhibiting apoptosis and neovascularization . Besides, Qin et al confirmed its repression on gastric cancer cell proliferation, survival and blockage of cell cycle at G2/M phase at 0.1, 10 and 1 mmol/l morphine.…”

“…Morphine is an opiate‐based drug by stimulating opioid receptor signalling in neurons, which is served as an analgesic to alleviate persistent pain caused by cancer all over the world . Based on many experiments of cancer cell lines and mouse models, some studies reported that morphine might even change cancer progression.…”

Could Perioperative Opioid Use Increase the Risk of Cancer Progression and Metastases?

“…Indeed, a recent study in a nasopharyngeal carcinoma (NPC) model demonstrated that low dose morphine can contribute to resistance to chemotherapy via inhibition of apoptotic and anti-angiogenic effects of cisplatin. 39 Thus strategies to inhibit the mitogenic activity of morphine without antagonizing its analgesic activity are required.…”

Radio-sensitizing effect of ethyl caffeate on nasopharyngeal carcinoma CNE-2 cell line

“…It has been reported that NPC distribution exhibits geographical characteristics, with presence mainly in Eastern and Southeastern Asia, and Northern Africa [2,3]. Epidemiological investigations have revealed that men are more susceptible to NPC than women [2].…”