白桦脂醇对宫颈癌小鼠自然杀伤细胞杀伤力及淋巴细胞增殖活性的影响

Effects of betulin on natural killer cell cytotoxicity and lymphocyte proliferative activity in mouse models of cervical cancer

摘要:

目的 探究白桦脂醇对宫颈癌小鼠自然杀伤（NK）细胞杀伤力及淋巴细胞增殖活性的影响。方法 通过皮下注射人宫颈癌HeLa细胞复制宫颈癌小鼠模型。将45只模型小鼠随机分为模型组、白桦脂醇组和白桦脂醇+SB203580组，每组15只。另取15只未做处理的小鼠作为对照组。白桦脂醇组和白桦脂醇+SB203580组白桦脂醇灌胃干预（100 mg/kg）。白桦脂醇+SB203580组通过腹腔注射SB203580（50 ng/kg）抑制p38通路。采用免疫组织化学染色检测细胞增殖。比较各组p38蛋白、NK细胞杀伤力及淋巴细胞增殖活性。结果 白桦脂醇组和白桦脂醇+SB203580组肿瘤体积和质量小于模型组（P <0.05），并且白桦脂醇+SB203580组肿瘤体积和质量小于白桦脂醇组（P <0.05）。白桦脂醇组和白桦脂醇+SB203580组免疫组织化学染色评分、p38蛋白相对表达量低于模型组（P <0.05），并且白桦脂醇+SB203580组免疫组织化学染色评分、p38蛋白相对表达量低于白桦脂醇组（P <0.05）。白桦脂醇组和白桦脂醇+SB203580组脾脏指数、NK细胞杀伤力、淋巴细胞增殖活性高于模型组（P <0.05），并且白桦脂醇+SB203580组脾脏指数、NK细胞杀伤力、淋巴细胞增殖活性高于白桦脂醇组（P <0.05）。结论 白桦脂醇通过抑制p38通路抑制宫颈癌细胞增殖，并提高NK细胞杀伤力和淋巴细胞增殖活性。

Abstract:

Objective To explore the effects of betulin on natural killer (NK) cell cytotoxicity and lymphocyte proliferative activity in mouse models of cervical cancer.Methods Mouse models of cervical cancer were established by subcutaneous injection of the human cervical cancer cell line HeLa, and a total of 45 mouse models were randomly divided into model group, betulin group and betulin+SB203580 group, each with 15 mice. Besides, another 15 untreated mice were set as a control group. Betulin was given via intragastric administration (100 mg/kg), while intraperitoneal injection of SB203580 (50 ng/kg) was given to inhibit the p38 pathway. The cell proliferation was detected by immunohistochemical staining. The protein expression of p38, NK cell cytotoxicity and lymphocyte proliferative activity were compared among groups.Results The volume and mass of tumors in the betulin group and the betulin+SB203580 group were smaller than those in the model group (P < 0.05), and they were even smaller in the betulin+SB203580 group relative to the betulin group (P < 0.05). The mmunoreactive score and the relative expression of p38 protein in the betulin group and the betulin + SB203580 group were lower than those in the model group (P < 0.05), and they were even lower in the betulin + SB203580 group relative to the betulin group (P < 0.05). The spleen index, NK cell cytotoxicity and lymphocyte proliferative activity were higher in the betulin group and the betulin + SB203580 group compared with the model group (P < 0.05), while these indicators were even higher in the betulin + SB203580 group than those in the betulin group (P < 0.05).Conclusions Betulin not only inhibits the proliferation of cervical cancer cells, but also improves NK cell cytotoxicity and the lymphocyte proliferative activity by suppressing the p38.