粘液瘤病毒“嗜侧群细胞现象”及联合化疗药物治疗胆囊癌的实验研究

Gallbladder cancer has chemotherapy-resistance. According to cancer stem cell theory, the ability to resist chemotherapeutics comes from side population cells. We have demonstrated that side population cells isolated from three cell strain have faster self-renewal rate, stronger invasiveness and superior chemotherapy-resistance than non side population cells. Myxoma virus specifically infects and vandalizes side population cells which just covered the deficiency of chemotherapeutics. Combination myxoma virus with chemotherapeutics was proved of practicability. We speculated that the "side population cells trend" of myxoma virus was correlated with the high expression of phosphorylated Akt and combination regimen could enhanced the anti-tumor effect against gallbladder cancer.This study aimed to validate the combination regimen was superior to virus or chemotherapeutics alone in treating gallbladder cancer. And we designed to explore the best practical order, dosage, interval time by building in situ mouse gallbladder cancer model. It is hoped to provide new data to the field of synthetic tumor treatment of gallbladder cancer.

胆囊癌对化疗不敏感，根据肿瘤干细胞理论，可能与其侧群细胞对化疗药物耐受密切相关。前期研究发现胆囊癌中的侧群细胞具有自我更新快、侵袭性高的干细胞特性，且化疗耐药性显著高于非侧群细胞。而粘液瘤病毒具有嗜侧群细胞现象，特异性地感染、杀伤侧群细胞，正好弥补传统化疗药物的不足，联合方案具有理论基础。我们认为MV病毒嗜SP细胞现象与其高表达磷酸化Akt相关，联合方案能提高对胆囊癌的抑癌效果。本课题拟通过体内外实验，验证联合方案较单独用药抑癌效果更好；并构建免疫健全小鼠的原位胆囊癌模型，探索联合方案的最佳注射顺序、注射剂量及间隔时间。本研究为胆囊癌的综合治疗提供新方向。

胆囊癌对化疗不敏感，根据肿瘤干细胞理论，可能与其侧群细胞对化疗药物耐受密切相关。本研究发现胆囊癌中的侧群细胞具有自我更新快、侵袭性高的干细胞特性，且化疗耐药性显著高于非侧群细胞。而粘液瘤病毒具有嗜侧群细胞现象，特异性地感染、杀伤侧群细胞。其嗜SP细胞现象与其高表达磷酸化Akt相关。因此MV病毒联合吉西他滨可以互相补充，提高对肿瘤的杀伤效果。体内实验证实先注射吉西他滨，2小时后注射MV病毒对裸鼠成瘤的杀伤效果最好。本课题拟通过体内外实验，明确MV病毒联合化疗药物对提供溶瘤效果的机制，并探索联合方案的最佳注射顺序、注射剂量及间隔时间。本研究为胆囊癌的综合治疗提供新方向。