加减行健汤联合化疗治疗胃癌术后的临床观察及其成分抗肿瘤增殖机制研究

发布时间：2018-06-03 13:08

本文选题：行健汤 + 胃癌　；参考：《南京中医药大学》2017年博士论文

【摘要】：研究目的:以孟河医派学术思想为指导,结合导师临床经验,通过临床对照研究,观察加减行健汤联合化疗,对比单纯化疗组,治疗胃癌术后脾胃气虚证患者的临床疗效及对生活质量的影响。研究其成分薯蓣皂苷抑制肿瘤细胞增殖的机制。研究方法:本研究分临床观察和实验研究两部分。临床观察部分:选择60例胃癌术后脾胃气虚证患者,随机分为对照组-单纯化疗组及治疗组-中药联合化疗组,观察周期3个月,观察两组治疗前后的中医症状、生活质量、肿瘤指标、淋巴细胞亚群变化,以及化疗后毒副反应,并统计分析结果。实验研究部分:首先,运用实时定量荧光PCR法检测胃癌组织中长链非编码RNAH19、HOTAIR、MALAT1的表达,选择表达量最高的HOTAIR,对比临床资料,说明HOTAIR的表达与临床病理因素之间的相关性。其次,用实时定量荧光PCR法检测胃癌细胞SGC-7901、HGC-27、MGC-803细胞株及正常黏膜上皮GES-1细胞株中三种长链非编码RNA的表达情况。选择MGC-803细胞及1ncRNAHOTAIR行下一步实验。用si-RNA下调HOTAIR的表达后,MTT法检测胃癌MGC-803细胞增殖情况,说明HOTAIR对于胃癌细胞的作用。第三步,研究薯蓣皂苷抗胃癌增殖机制。运用MTT法检测薯蓣皂苷对于胃癌MGC-803细胞的抑制作用。用si-HOTAIR、薯蓣皂苷同时干预胃癌MGC-803细胞,对比阴性对照组,用实时定量PCR法检测胃癌细胞中的HOTAIR相对表达量,MTT法、细胞克隆形成实验观察胃癌细胞增殖情况,研究薯蓣皂苷的抗胃癌增殖机制。研究结果:临床观察部分:有效评价患者共57例,治疗组29例,对照组28例。经过治疗,治疗组在中医症状改善方面优于对照组,尤其是在食少纳呆、体倦乏力、食后腹胀、大便异常、神疲懒言、面色萎黄、排便无力方面,经过治疗,治疗组优于对照组,两组治疗后比较有统计学差异(P0.05)。生活质量评价方面,EORTC QLQ-ST052量表评分方面,治疗组治疗后在躯体功能、角色功能、情绪功能、总健康、疲倦、失眠、食欲丧失、便秘、腹泻、吞咽困难、返流、进食受限等方面较对照组治疗后改善,两组治疗后比较有统计学差异(P0.05)。FACT-G评分量表,治疗组经过治疗,在生理状况及功能状况改善方面优于对照组,有统计学差异(P0.05)。经过治疗,治疗组在淋巴细胞亚群改善方面优于对照组,两组治疗后比较有统计学差异(P0.05)。两组在肿瘤指标变化方面无统计学差异(P0.05)。PFS方面,随访日期为2016年10月30日,中药联合化疗组中位进展时间8.0±0.21个月,化疗组中位进展时间为7.0±0.65个月,两组PFS时间无统计学差异(P0.05)。毒副反应方面,治疗前后两组在骨髓抑制、胃肠道反应、肝功能异常、神经毒性、皮肤反应方面无统计学差异(P0.05)。实验部分:在胃癌组织中长链非编码RNAHOTAIR、H19、MALAT-1均高表达。其中,HOTAIR表达与胃癌的分期、淋巴结转移、浸润深度相关。胃癌MGC-803、SGC-7901、HGC-27细胞株中,HOTAIR、MALAT-1也高表达。选择胃癌MGC-803细胞和HOTAIR进行后续实验。用si-RNA下调胃癌MGC-803细胞中的HOTAIR表达后,胃癌细胞增殖受到抑制。可以认为HOTAIR高表达可促进胃癌MGC-803细胞增殖。薯蓣皂苷为加减行健汤的抗肿瘤成分之一。用薯蓣皂苷干扰胃癌MGC-803细胞后,胃癌MGC-803细胞中的HOTAIR表达量下降,胃癌细胞增殖也受到抑制。认为通过下调胃癌细胞中HOTAIR的表达从而抑制胃癌细胞增殖是薯蓣皂苷抗肿瘤的可能机制。结论:加减行健汤配合化疗能起到提高生活质量,改善症状,提高机体免疫功能的作用。实验研究证实,其抗肿瘤成分薯蓣皂苷可能通过下调胃癌细胞中HOTAIR的表达从而抑制胃癌细胞增殖。
[Abstract]:Objective: To observe the clinical curative effect and the effect on the quality of life of the patients with spleen and stomach qi deficiency after the operation of gastric cancer and study the mechanism of diosgenin to inhibit the proliferation of tumor cells by combining the clinical experience of the Mencius medical school and combining the clinical experience of the tutor to observe the combined chemotherapy and subtraction of the combination chemotherapy and subtraction of the combination chemotherapy and the simple chemotherapy group. Research methods: This study was divided into two parts of clinical observation and experimental study. Clinical observation part: select 60 cases of spleen and stomach qi deficiency after gastric cancer surgery, randomly divided into control group - simple chemotherapy group and treatment group - Chinese medicine combined chemotherapy group, observe the period of 3 months, observe the symptoms of traditional Chinese medicine, quality of life, tumor index, lymphocyte subgroup before and after treatment of two groups. Group changes, toxicity and side effects after chemotherapy, and statistical analysis results. Experimental research part: first, real-time quantitative fluorescence PCR method was used to detect the expression of long chain noncoding RNAH19, HOTAIR, MALAT1 in gastric cancer tissue, and the highest expression of HOTAIR was selected. The correlation between the expression of HOTAIR and the clinicopathological factors was compared. Secondly, the correlation between the expression of HOTAIR and the clinicopathological factors was compared. The expression of three long chain non coded RNA in gastric cancer cells SGC-7901, HGC-27, MGC-803 cell lines and normal mucosal epithelial GES-1 cell lines was detected by real-time quantitative fluorescence PCR. The next experiment of MGC-803 cells and 1ncRNAHOTAIR was selected. The proliferation of gastric cancer MGC-803 cells was detected by si-RNA downregulation and MTT method was used to detect the proliferation of gastric cancer MGC-803 cells. The third step was to study the anti gastric cancer proliferation mechanism of diosgenin. The inhibitory effect of diosgenin on gastric cancer MGC-803 cells was detected by MTT. Si-HOTAIR and Diosgenin were used to interfere with the MGC-803 cells of gastric cancer at the same time, and the negative control group was compared with the negative control group. The relative expression of HOTAIR in gastric cancer cells was detected by real-time quantitative PCR, MTT Method, cell clone formation test to observe the proliferation of gastric cancer cells and study the anti gastric cancer proliferation mechanism of diosgenin. The results of the study: clinical observation part: the effective evaluation of 57 patients, 29 cases in the treatment group and 28 cases in the control group. After treatment, the treatment group is better than the control group in the improvement of Chinese medicine symptoms, especially in the diet, body fatigue and fatigue. After the abdominal distention, abnormality of stool, deity laziness, pale yellow and defecation, the treatment group was better than the control group. The two groups were compared with the control group (P0.05). The quality of life evaluation, the EORTC QLQ-ST052 scale score, the treatment group after treatment in the body function, function, emotional function, total health, fatigue, insomnia, food Loss of desire, constipation, diarrhea, dysphagia, reflux, food restriction, and other aspects of improvement after treatment compared with the control group, the two groups after treatment had a statistically significant difference (P0.05).FACT-G score scale, the treatment group after treatment, the physiological status and functional status improvement is better than the control group, there is a statistical difference (P0.05). After treatment, the treatment group in lymphatic thin. The improvement of cell subgroup was better than that of the control group. The two groups had statistical difference after treatment (P0.05). There was no statistical difference between the two groups (P0.05).PFS, the date of follow-up was October 30, 2016, the median progress time of the combination chemotherapy group was 8 + 0.21 months, the median progression time of the chemotherapy group was 7 + 0.65 months, and the two groups of PFS There was no statistical difference (P0.05). In the side effects, there was no statistical difference between the two groups in bone marrow suppression, gastrointestinal reaction, liver dysfunction, neurotoxicity, and skin reaction (P0.05). Experimental part: the high expression of long chain non coded RNAHOTAIR, H19, MALAT-1 in gastric cancer tissues. Among them, HOTAIR expression and gastric carcinoma staging, lymph nodes Metastasis, infiltration depth related. Gastric cancer MGC-803, SGC-7901, HGC-27 cell lines, HOTAIR, MALAT-1 also high expression. Select gastric cancer MGC-803 cells and HOTAIR for follow-up experiments. The proliferation of gastric cancer cells was inhibited after si-RNA down-regulation of HOTAIR expression in gastric cancer MGC-803 cells. It can be considered that HOTAIR high expression can promote the proliferation of gastric cancer MGC-803 cells. Diosgenin is one of the antineoplastic ingredients in the addition of diosgenin. After diosgenin interferes with gastric cancer MGC-803 cells, the expression of HOTAIR in gastric cancer MGC-803 cells is decreased and the proliferation of gastric cancer cells is inhibited. It is considered that the possible mechanism of diosgenin anti tumor by reducing the expression of HOTAIR in gastric cancer cells and inhibiting the proliferation of gastric cancer cells is the possible mechanism of diosgenin antitumor. Conclusion: the addition and subtraction of Jian Jian decoction combined with chemotherapy can improve the quality of life, improve the symptoms and improve the immune function of the body. The experimental study has proved that the antitumor component of diosgenin may inhibit the proliferation of gastric cancer cells by down regulating the expression of HOTAIR in gastric cancer cells.
【学位授予单位】：南京中医药大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R735.2

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