清热利湿外治法对宫颈癌荷瘤裸鼠抗肿瘤作用与MARK信号通路的关系

Relationship between anti-tumor effect and MARK signaling pathway in nude mice bearing cervical cancer treated with Qingre Lishi

关键词:  宫颈癌  清热利湿法  Siha  裸鼠  移植瘤

Key words:  cervical carcinoma  Qingre Lishi  Siha  nude mice  transplanted tumor

摘要:

[目的] 探讨清热利湿外治法对HPV（+）宫颈癌荷瘤裸鼠模型抗肿瘤作用及对ERK及P38/MAPK信号通路的影响。[方法] 建立人宫颈癌Siha细胞荷瘤裸鼠皮下移植瘤模型，裸鼠成瘤后，按随机数字表法分为5组，即顺铂组、空白对照组和清热利湿外治法高剂量（0.942 8 mg/kg）、中剂量（0.471 4 mg/kg）、低剂量组（0.235 7 g/kg），连续用药观察28天。停药24小时后处死裸鼠，完整取出肿瘤组织，测量肿瘤体积及体质量，计算抑瘤率。将肿瘤组织切片后，HE染色法观察肿瘤的形态学变化，运用免疫组化SP的方法，检测肿瘤组织中的p-ERK及p-p38蛋白表达水平。[结果] 清热利湿外治法用药组的移植瘤体积均明显小于空白对照组（P<0.05），高、中、低剂量组抑瘤率分别为36.23%、31.24%和14.94%；HE染色法显示清热利湿外治法用药组裸鼠的移植瘤组织出现明显坏死改变；清热利湿外治法中剂量、高剂量治疗组的p-ERK及p-p38蛋白水平明显下降，与空白对照组比较差异有统计学意义（P<0.05）。[结论] 清热利湿外治法对人宫颈癌Siha细胞移植瘤的生长具有明显抑制作用；其作用机制可能与下调ERK/P38 MARK（丝裂原活化蛋白激酶）信号转导通路的磷酸化水平有关。

Abstract:

[Objective] To investigate the anti-tumor effect and the effect on ERK and P38/MAPK signaling pathway of HPV (+) cervical cancer-bearing nude mice model treated with clearing heat and removing dampness.[Methods] Human cervical cancer Siha cells were transplanted subcutaneously into nude mice. The nude mice were divided into 5 groups according to random numerical table:cisplatin group, blank control group and cypress gel high dose (0.94 28 mg/kg), and the mice were divided into 5 groups:cisplatin group, blank control group and cypress gel high dose (0.942 8 mg/kg). Middle dose (0.471 4 mg/kg), low dose group (0.235 7 g/kg) were observed for 28 days. After 24 hours, the nude mice were killed and the tumor tissue was taken out completely. The tumor volume and body mass were measured and the tumor inhibition rate was calculated. The morphological changes of the tumor were observed by HE staining and the expression levels of p-ERK and pA38 protein in the tumor tissue were detected by immunohistochemical SP method after the tumor tissue was sliced.[Results] The volume of transplanted tumor in the treatment group was significantly smaller than that in the blank control group (P<0.05). The tumor inhibition rates in the middle and low dose groups were 36.23%, 31.24% and 14.94%, respectively, and the tumor inhibition rates in the middle and low dose groups were 36.23%, 31.24% and 14.94%, respectively. HE staining showed that there were obvious necrotic changes in the transplanted tumor tissue of mice treated by clearing heat and removing dampness. In the middle and high dose groups of clearing heat and removing dampness, the levels of p-ERK and pA38 protein were significantly decreased.[Conclusion] The method of clearing heat and removing dampness can significantly inhibit the growth of human cervical cancer Siha cells transplanted tumor. The mechanism may be related to the down-regulation of phosphorylation level of ERK/P38 MARK signal transduction pathway.