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.
Highlights
IntroductionCisplatin forms highly reactive, charged, platinum complexes that bind to nucleophilic groups, such as GC-rich sites in DNA
At last we investigated whether morphine was able to affect the sensitivity of CNE-2 cells to cisplatin chemotherapy
Most Nasopharyngeal carcinoma (NPC) patients receive morphine to relieve severe pain induced by the cancer itself, bone metastasis, radiotherapy or chemotherapy
Summary
Cisplatin forms highly reactive, charged, platinum complexes that bind to nucleophilic groups, such as GC-rich sites in DNA. This induces intrastrand and interstrand DNA cross-links as well as DNA-protein cross-links, which inhibit cell growth and result in apoptosis. Morphine produces strong analgesic effects by stimulating opioid receptor signaling in neurons. In addition to these well-recognized effects, various studies have suggested that morphine elicits a variety of biological effects that appear to be independent of its analgesic properties and may affect cell survival or proliferation[12]. We aimed to investigate the role of morphine in NPC chemotherapy using CDDP in vitro and in vivo
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