扶正健脾方联合化疗通过PI3K/AKT信号通路对肿瘤转移微环境的影响
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摘要
目的:观察扶正健脾方对PI3K/AKT信号通路的影响,分析该方抑制肿瘤转移的作用机制及途径。方法:建立裸鼠结肠癌原位移植高转移模型,分为模型组、5-氟尿嘧啶组、奥沙利铂组、5-氟尿嘧啶+奥沙利铂组、扶正健脾方+5-氟尿嘧啶+奥沙利铂组及谷氨酰胺+5-氟尿嘧啶+奥沙利铂组,每组10只;原位移植手术第3天开始,均按照0.01 mL·g~(-1)开始腹腔注射给药,第17天到第38天共21 d,连续灌胃处理。第39天仅提供水禁食,第40天处死取材。观察裸鼠体质量和肠道肿瘤的质量,采用免疫组织化学法、Real-Time PCR、Western Blot检测肠道肿瘤组织中AKT、PI3K的表达。结果:①裸鼠体质量和肠道肿瘤质量:各组裸鼠体质量比较,差异无统计学意义(P>0.05);各组肠道肿瘤质量比较,差异有统计学意义(P<0.05),与其他组比较,扶正健脾方+5-FU+奥沙利铂对肿瘤质量有影响,能使瘤体明显缩小(P<0.05),但与谷氨酰胺+5-FU+奥沙利铂组比较,差异无统计学意义(P>0.05)。②PI3K/AKT表达:扶正健脾方+5-氟尿嘧啶+奥沙利铂组与模型组、5-氟尿嘧啶组、奥沙利铂组比较,明显下调PI3K、AKT表达(P<0.05);扶正健脾方+5-氟尿嘧啶+奥沙利铂组与谷氨酰胺+5-氟尿嘧啶+奥沙利铂组PI3K、AKT表达比较,差异无统计学意义(P>0.05)。结论:健脾扶正方联合化疗能有效控制瘤体大小,有效降低PI3K、AKT的表达;与谷氨酰胺联合化疗疗效相当,证实中药扶正健脾方可通过PI3K/AKT信号通路抑制肿瘤转移产生。
Objective:To observe the effect of Fuzheng Jianpi Recipe on PI3 K/AKT signaling pathway and to study its mechanism and pathway in inhibiting tumor metastasis.Methods:A high-metastasis model of orthotopic transplantation of colon cancer in nude mice was established,which was divided into model group,5-fluorouracil group,oxaliplatin group,5-fluorouracil+oxaliplatin group,Fuzhengjianpi+5-fluorouracil+saliplatin group and the glutamine+5-fluorouracil+oxaliplatin group,with 10 mice in each group.Three days after the orthotopic transplantation,the intraperitoneal injection was started according to the dosage of 0.01 mL·g~(-1).From the 17 th day to the 38 th day,a total of 21 days,continuous gavage treatment.On the 39 th day,only water was provided,and on the 40 th day,mice were sacrificed.The quality of nude mice and the quality of intestinal tumors were observed.The expressions of AKT and PI3 K in intestinal tumor tissues were detected with immunohistochemistry,Real-time PCR and Western blot.Results:(1) Body mass and intestinal tumor quality in nude mice:There was no significant difference in the body weight of nude mice in each group(P>0.05).The difference between the quality of intestinal tumors in each group was statistically significant.Compared with other groups,the+5-FU+L-OHP group had an effect on tumor quality,which significantly reduced the tumor size(P<0.05),but compared with the glutamine+5-FU+L-OHP group,the difference was not statistically significant(P>0.05).(2) PI3 K/AKT expression:PI3 K/AKT expression in Fuzheng Jianpi Recipe+5-fluorouracil+oxaliplatin group was significantly down-regulated compared with model group,5-fluorouracil group and oxaliplatin group(P<0.05).The difference of PI3 K and AKT between the group+5-fluorouracil+oxaliplatin group and glutamine+5-fluorouracil+oxaliplatin group was not statistically significant(P>0.05).Conclusion:Jianpi Fuzheng Recipe combined with chemotherapy can effectively control the tumor size and effectively reduce the expression of PI3 K and AKT.It is equivalent to the efficacy of glutamine combined with chemotherapy.It is confirmed that Fuzheng Jianpi Recipe can inhibit tumor metastasis through PI3 K/AKT signaling pathway.
Objective:To observe the effect of Fuzheng Jianpi Recipe on PI3 K/AKT signaling pathway and to study its mechanism and pathway in inhibiting tumor metastasis.Methods:A high-metastasis model of orthotopic transplantation of colon cancer in nude mice was established,which was divided into model group,5-fluorouracil group,oxaliplatin group,5-fluorouracil+oxaliplatin group,Fuzhengjianpi+5-fluorouracil+saliplatin group and the glutamine+5-fluorouracil+oxaliplatin group,with 10 mice in each group.Three days after the orthotopic transplantation,the intraperitoneal injection was started according to the dosage of 0.01 mL·g~(-1).From the 17 th day to the 38 th day,a total of 21 days,continuous gavage treatment.On the 39 th day,only water was provided,and on the 40 th day,mice were sacrificed.The quality of nude mice and the quality of intestinal tumors were observed.The expressions of AKT and PI3 K in intestinal tumor tissues were detected with immunohistochemistry,Real-time PCR and Western blot.Results:(1) Body mass and intestinal tumor quality in nude mice:There was no significant difference in the body weight of nude mice in each group(P>0.05).The difference between the quality of intestinal tumors in each group was statistically significant.Compared with other groups,the+5-FU+L-OHP group had an effect on tumor quality,which significantly reduced the tumor size(P<0.05),but compared with the glutamine+5-FU+L-OHP group,the difference was not statistically significant(P>0.05).(2) PI3 K/AKT expression:PI3 K/AKT expression in Fuzheng Jianpi Recipe+5-fluorouracil+oxaliplatin group was significantly down-regulated compared with model group,5-fluorouracil group and oxaliplatin group(P<0.05).The difference of PI3 K and AKT between the group+5-fluorouracil+oxaliplatin group and glutamine+5-fluorouracil+oxaliplatin group was not statistically significant(P>0.05).Conclusion:Jianpi Fuzheng Recipe combined with chemotherapy can effectively control the tumor size and effectively reduce the expression of PI3 K and AKT.It is equivalent to the efficacy of glutamine combined with chemotherapy.It is confirmed that Fuzheng Jianpi Recipe can inhibit tumor metastasis through PI3 K/AKT signaling pathway.
引文
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[2]孙燕,主编.内科肿瘤学[M].北京:人民卫生出版社,2001:623-624.
[3]吴婷婷,王燕莹,钟薏,等.肠益煎对裸鼠结肠癌移植瘤抑瘤作用的实验研究[J].现代中西医结合杂志,2015,24(12):1267-1269.
[4]刘丹.小檗碱缓解伊立替康对肠道免疫系统损伤的机制研究[D].大连:大连医科大学,2014.
[5]海艳洁,卢林,丁艳波.健脾渗湿汤对晚期大肠癌患者肠道微生态的影响[J].中国药师,2010,13(11):1545-1547.
[6]许文捷,薛志祥,李财宝.复元方对围手术期胃肠道肿瘤患者肠黏膜屏障功能的影响[J].中国中西医结合外科杂志,2010,16(4):418-420.
[7]邓皖利,吕书勤,任小娟,等.益气复生方对胃癌原位移植瘤小鼠肠黏膜屏障的影响[J].世界华人消化杂志,2013,21(11):951-956.
[8]LUPPI F,LONGO A M,DE BOERW I,et al.Interleukin-8 stim-ulates cell proliferation in non small cell lung cancer through epidermal growth factor receptor transactivation[J].Lung Cancer,2007,56(1):25-33.
[9]MURPHY C,MCGURK M,PETTIGREW J,et al.Nonapical and cytoplasmic expression of interleukin-8 CxcR1,and CxcR2 correlates with cell proliferation and microvessel density in prostate cancer[J].Clin Can Res,2005,11(11):4117-4127.
[10]胡蕾,姜汉国.PI3K/AKT信号转导通路与肿瘤转移及其机制的研究进展[J].医学综述,2006,12(22):1375-1377.
[11]付淑娟,钟薏,周张杰,等.肿瘤炎症与免疫抑制微环境研究进展[J].河北中医,2016,38(12):1904-1908.
[12]刘卫仁.免疫微环境及代谢在肝细胞癌侵袭与转移中的作用研究[D].上海:复旦大学,2014.