疏肝益肾方治疗乳腺癌内分泌耐药的临床观察及对外泌体miR-221的影响

Clinical observation of Shugan Yishen Recipe on the patients of endocrine resistance in breast cancer and effects on exosome miR-221

目的观察疏肝益肾方治疗乳腺癌内分泌耐药患者的无进展生存期(PFS)、生活质量和中医证候评分变化,探讨疏肝益肾方对乳腺癌内分泌耐药患者血清外泌体微RNA-221(miR-221)及磷酸酶与张力蛋白同源物(PTEN)表达水平的影响。方法采用随机对照的方法。(1)共纳入60例乳腺癌内分泌耐药冲任失调证患者,对照组(西医规范治疗)30例,试验组(疏肝益肾方联合西医规范治疗)30例。疏肝益肾方每日1剂,早晚分服,干预至疾病进展、死亡或研究结束,随访观察PFS、乳腺癌患者生命质量测定量表(FACT-B)评分和中医证候评分变化。(2)于每组各选择5例进行探索性研究,分别在入组及入组2周时采集外周血,检测血清外泌体miR-221和PTEN表达水平。结果2组基线平衡。(1)试验组中位无进展生存期(mPFS)为8.000(95%CI:2.814~13.186)个月,对照组mPFS为4.000(95%CI:2.271~5.729)个月。2组患者治疗前后FACT-B评分差比较,差异无统计学意义。试验组中医证候评分改善率优于对照组(P<0.05)。肿瘤大小是乳腺癌内分泌耐药患者复发的危险因素。(2)与治疗前比较,试验组治疗后血清外泌体miR-221水平下调(P<0.05),PTEN表达水平上调(P<0.05),而对照组治疗前后差异无统计学意义。结论疏肝益肾方能延长乳腺癌内分泌耐药患者的PFS,改善中医证候,其作用机制可能是通过调控外泌体miR-221/PTEN轴逆转乳腺癌内分泌耐药。

Objective We aimed(i)to observe the changes in progression free survival(PFS),quality of life,and traditional Chinese medicine(TCM)syndrome score in the treatment of patients with endocrine resistance in breast cancer,and(ii)to investigate the effect Shugan Yishen(dispersing stagnated liver qi and invigorating kidney qi)Recipe on serum exosome microRNA-221(miR-221)and phosphatase and tensin homolog(PTEN)expression levels in patients with endocrine resistance in breast cancer.Methods A randomized controlled was used to study a total of 60 patients with endocrine resistance in breast cancer with a pattern of thoroughfare-controlling vessels disharmony.The experimental group adopted the treatment of Shugan Yishen Recipe(be taken after decocted by water twice a day)combined with standardized treatment of western medicine,and the control group adopted only standardized treatment of western medicine(30 cases in each group).Observe patients until disease progression,death,or the end of study.Follow-up to observe PFS and assess Functional Assessment of Cancer Therapy-Breast(FACT-B)scores and changes in TCM syndrome scores.Five patients from each group were selected for exploratory studies,and peripheral blood was collected at the time of enrollment and 2 weeks after enrollment respectively,to detect serum exosome miR-221 expression levels and serum PTEN expression levels.Results Baseline was consistent between the two treatment groups.(ⅰ)The intermediate PFS(mPFS)in the trial group was 8.000(95%CI:2.814-13.186)months,and the mPFS in the control group was 4.000(95%CI:2.271-5.729)months.The differences of FACT-B scores of before and after treatment of both groups were not significant.The improvement rate of TCM syndrome score of the experimental group was better than that of the control group(P<0.05).Tumor size was a risk factor for recurrence in patients with endocrine resistance in breast cancer.(ⅱ)Serum exosome miR-221 levels were found to be significantly downregulated after treatment in the experimental group than before treatment(P<0.05)and not significantyly lowered in the control group.The PTEN expression level in the experimental group was significantly higher than before treatment(P<0.05),and the difference between before and after treatment in the control group was not obvious.Conclusion Shugan Yishen Recipe can prolong PFS in patients with endocrine resistance in breast cancer and improve TCM syndrome.Its mechanism may be to reverse endocrine resistance of breast cancer by regulating the exosome miR-221/PTEN axis.