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

• Published in: Scientific reports Vol. 6; no. 1; p. 18706
• Main Authors: Cao, Long-Hui, Li, Hui-Ting, Lin, Wen-Qian, Tan, Hong-Ying, Xie, Lan, Zhong, Zhong-Jian, Zhou, Jian-Hua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.01.2016; Nature Publishing Group
• Subjects: 13; 13/2; 13/51; 692/308/409; 692/700/565/1436/1437; 692/700/565/1436/99; Analgesics; Animal models; Animals; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Bcl protein; Bcl-2 protein; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Carcinoma; Caspase; Caspase-3; Caspases - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemoresistance; Cisplatin; Cisplatin - pharmacology; Cytotoxicity; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Antagonism; Gene Expression; Humanities and Social Sciences; Humans; Metastases; Mice; Mice, Nude; Morphine; Morphine - pharmacology; multidisciplinary; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - drug therapy; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Opioids; Pain; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Science; Throat cancer; Tumor Burden; Vascularization; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep18706

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.