Agonists Specific for κ-Opioid Receptor Induces Apoptosis of HCC Cells Through Enhanced Endoplasmic Reticulum Stress

• DOI: 10.3389/fonc.2022.844214
• Publication Date: 2022-03-31T11:50:53Z
• Authors: Mengyuan Tan; Hanyu Wang; Cheng Gao; Zhen Jiang; Ying Yin; Ruyi Xing; Ling Hu; Jiegou Xu; Min Zhang; Yanhu Xie
• Keywords: Oncology; apoptosis; PERK pathway; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; hepatocellular carcinoma; opioid agonists; opioid receptors; RC254-282; 3. Good health

Cancer pain is an important factor affecting life quality of patients especially in the advanced stage and relieving one fundamental strategies for cancer treatment. Opioids such as morphine are most widely used clinics. However, they have been reported to be associated with occurrence development several types cancer. Thus, search opioid that has analgesic effect can retard progress simultaneously critical management. In this study, we first examined expression μ κ (MOR KOR) cell lines tumor tissues hepatocellular carcinoma (HCC), a malignant high mortality, then compared effects receptors-specific agonists on phenotypes HCC cells vitro growth xenograft mouse model. KOR MOR were found highly expressed tissues. The KOR-specific agonist U50488h, oxycodone (agonist both MOR) MOR-specific inhibited proliferation, while only U50488h suppressed colony formation migration cells. oxycodone, but not morphine, induced apoptosis. Further detection PERK, GRP78 CHOP revealed PERK signaling was upregulated by treatment inhibitor GSK2656157 partially reversed promotion apoptosis inhibition proliferation indicating endoplasmic reticulum stress its suppressing phenotypes. Similar results, significantly reduced administration caspase-3 up-regulated detected immunohistochemistry western blotting. Taken together, our results activation vivo, did effect. Because their dual roles relief suppression phenotypes, opioids act should considered choice