Ex vivo nonviral gene delivery of μ-opioid receptor to attenuate cancer-induced pain.
Ex vivo nonviral gene delivery of μ-opioid receptor to attenuate cancer-induced pain.
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DOI：
10.1097/j.pain.0000000000000750
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发表时间：
2017-03
期刊：
影响因子：
7.4
通讯作者：
Schmidt BL
中科院分区：
文献类型：
--
作者：
Yamano S;Viet CT;Dang D;Dai J;Hanatani S;Takayama T;Kasai H;Imamura K;Campbell R;Ye Y;Dolan JC;Kwon WM;Schneider SD;Schmidt BL
病毒介导的基因传递显示出治疗慢性疼痛的希望。然而，病毒载体具有细胞毒性。为了避免病毒介导的基因递送的毒性和局限性，我们开发了一种新型的非病毒杂交载体：用组氨酸和半胱氨酸残基修饰的HIV-1达特肽序列与阳离子脂质结合。该载体在包括HSC-3（人舌鳞状细胞癌）在内的癌细胞系中具有高转染效率和很小的细胞毒性，并且相对于HGF-1（人牙龈成纤维细胞）细胞在HSC-3中表现出差异表达（~45倍）。我们使用非病毒载体与μ-阿片受体基因OPRM 1一起抑制癌症，作为治疗癌症引起的疼痛的新方法。在用OPRM 1转染HSC-3细胞后，通过将转染的HSC-3细胞接种到无胸腺小鼠的后爪或舌中来建立癌症小鼠模型，以确定OPRM 1转染的镇痛潜力。与对照小鼠相比，具有表达OPRM 1的HSC-3肿瘤的小鼠表现出显著的抗伤害感受。局部纳洛酮给药可逆转该效应。我们定量了HSC-3细胞的β-内啡肽分泌，并显示用OPRM 1转染的HSC-3细胞比对照HSC-3细胞分泌显著更多的β-内啡肽。这些发现表明，靶向癌症微环境的OPRM 1基因的非病毒递送在临床前癌症模型中具有镇痛作用，并且非病毒基因递送是癌症疼痛的潜在治疗方法。
Virus-mediated gene delivery shows promise for treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel non-viral 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 non-viral 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 to 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 non-viral delivery of the OPRM1 gene targeted to the cancer microenvironment has an analgesic effect in a preclinical cancer model, and non-viral gene delivery is a potential treatment for cancer pain.
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影响因子：
6.1
作者：
Goins, William F.;Cohen, Justus B.;Glorioso, Joseph C.
通讯作者：
Glorioso, Joseph C.
HSV介导的白介素4在背根神经神经元中的表达减轻了神经性疼痛。
影响因子：
3.3
作者：
Hao S;Mata M;Glorioso JC;Fink DJ
通讯作者：
Fink DJ
影响因子：
11.2
作者：
Hao, SG;Mata, M;Fink, DJ
通讯作者：
Fink, DJ
影响因子：
12.4
作者：
Liu, J;Wolfe, D;Fink, DJ
通讯作者：
Fink, DJ
影响因子：
3.3
作者：
Gelsinger, Paul;Shamoo, Adil E.
通讯作者：
Shamoo, Adil E.