Ex vivo nonviral gene delivery of μ-opioid receptor to attenuate cancer-induced pain. Issue 2 (February 2017)

• Record Type: Journal Article
• Authors: Yamano, Seiichi; Viet, Chi T.; Dang, Dongmin; Dai, Jisen; Hanatani, Shigeru; Takayama, Tadahiro; Kasai, Hironori; Imamura, Kentaro; Campbell, Ron; Ye, Yi; Dolan, John C.; Kwon, William Myung; Schneider, Stefan D.; Schmidt, Brian L.
• Is Part Of: Pain. Volume 158:Issue 2(2017)
• Publication Date: 2017-02
• Subjects: Cancer pain -- Gene delivery -- μ-opioid receptor -- OPRM1 -- Oral squamous cell carcinoma; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000000750
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 (∼45-fold) relative to HGF-1 (human gingival fibroblasts) cells. We used the nonviral vector to transfect cancer with OPRM1, the μ-opioid receptor gene, as a novel method for treating cancer-induced pain. After HSC-3 cells were transfected with OPRM1, a cancer mouse model was created by inoculating the transfected HSC-3 cells into the hind paw or tongue of athymic mice to determine the analgesic potential of OPRM1 transfection. Mice with HSC-3 tumors expressing OPRM1 demonstrated significant antinociception compared with control mice. The effect was reversible with local naloxone administration. We quantified β-endorphin secretion from HSC-3 cells and showed that HSC-3 cells transfected with OPRM1 secreted significantly more β-endorphin than control HSC-3 cells. These findings indicate that nonviral delivery of the OPRM1 gene targeted to the cancer microenvironment has an analgesic effect in a preclinical cancer model, and nonviral gene delivery is a potential treatment for cancer pain. Abstract : We demonstrate that expression of the gene for the μ-opioid receptor in cancer using a nonviral vector reverses cancer pain.