中药圣和散对三阴乳腺癌术后复发转移率的影响
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摘要
目的:观察圣和散辨证治疗对三阴乳腺癌患者手术联合放化疗后复发、转移率的影响。方法:168例I-IIIC期三阴乳腺癌术后患者随机分为治疗组和对照组,治疗组采用圣和散辨证治疗联合放化疗,对照组仅采用相同放化疗方案。两组患者术前和术后1、3月采用流式细胞仪检测T淋巴细胞亚群(CD~+_3, CD~+_4, CD~+_8, CD_4/CD_8)和自然杀伤(NK)细胞的活性,实时荧光定量PCR检测血清中miR-34a表达,酶联免疫吸附试验检测血清乳酸脱氢酶A(LDHA)的表达。结果:随访65～98个月,中位随访时间72个月。治疗组5年无病生存率和总生存率分别为75.0%和76.2%,明显优于对照组的60.7%和64.3%(P<0.05);治疗组复发转移率为23.8%,明显低于对照组的41.7%(P<0.05)。同时,接受圣和散辨证治疗明显增强miR-34a表达,抑制LDHA活性,患者的免疫功能指标CD~+_4、CD_4/CD_8和NK活性均明显优于对照组(P<0.01)。结论:圣和散辨证加减能明显提高miR-34a表达和机体免疫功能,抑制糖酵解,降低三阴乳腺癌术后复发转移,提高远期生存率。
Objective: To investigate the effects of Shenghe Powder(SHP, optimized treatment based on evidence of syndrome typing) combined with chemoradiotherapy for postoprative triple-negative breast cancer.Methods:Totally 168 patients with I-III C stage triple-negative breast cancer were randomly divided into treatment group and control group. The treatment group was treated with Shenghe Powder and chemoradiotherapy. The control group received chemoradiotherapy alone. T cell subsets(CD~+_3, CD~+_4, CD~+_8, CD~+_4/CD~+_8) and natural killer(NK) cells were determined by flow cytometry;concurrent serum miR-34 a expression was measured by Real-time PCR and serum LDHA was determined by enzyme linked immunosorbent assay at 1 day before surgery,1 and 3 months after surgery. Disease free survival(DFS), overall survival(OS), relapse and metastasis were observed in the two groups.Results: All patients were followed-up for 65 to 98 months,with the median follow-up of 72 months.The 5 years DFS and OS in the treatment group were 75.0% and 76.2% respectively, significantly higher than 60.7% and 64.3% in the control group(P<0.05). The recurrence and metastasis rate in the treatment group was 23.8%, which was significantly lower than 41.7% in the control group(P<0.05).In comparison to the control group, the SHP syndrome differentiation and treatment was markedly increased the levels of miR-34 a,CD~+_3, CD~+_4, CD~+_4/CD~+_8 and NK cells and inhibited the LDHA expression. Conclusion: The present study provides evidence that Shenghe Powder can markedly inhibit the recurrence and metastasis of triple-negative breast cancer, improve the long-term survival rate by miR-34 a and LDHA transformed contributing to immunity and metabolic reprogramming.
Objective: To investigate the effects of Shenghe Powder(SHP, optimized treatment based on evidence of syndrome typing) combined with chemoradiotherapy for postoprative triple-negative breast cancer.Methods:Totally 168 patients with I-III C stage triple-negative breast cancer were randomly divided into treatment group and control group. The treatment group was treated with Shenghe Powder and chemoradiotherapy. The control group received chemoradiotherapy alone. T cell subsets(CD~+_3, CD~+_4, CD~+_8, CD~+_4/CD~+_8) and natural killer(NK) cells were determined by flow cytometry;concurrent serum miR-34 a expression was measured by Real-time PCR and serum LDHA was determined by enzyme linked immunosorbent assay at 1 day before surgery,1 and 3 months after surgery. Disease free survival(DFS), overall survival(OS), relapse and metastasis were observed in the two groups.Results: All patients were followed-up for 65 to 98 months,with the median follow-up of 72 months.The 5 years DFS and OS in the treatment group were 75.0% and 76.2% respectively, significantly higher than 60.7% and 64.3% in the control group(P<0.05). The recurrence and metastasis rate in the treatment group was 23.8%, which was significantly lower than 41.7% in the control group(P<0.05).In comparison to the control group, the SHP syndrome differentiation and treatment was markedly increased the levels of miR-34 a,CD~+_3, CD~+_4, CD~+_4/CD~+_8 and NK cells and inhibited the LDHA expression. Conclusion: The present study provides evidence that Shenghe Powder can markedly inhibit the recurrence and metastasis of triple-negative breast cancer, improve the long-term survival rate by miR-34 a and LDHA transformed contributing to immunity and metabolic reprogramming.
引文
[1] Harbeck N, Gnant M. Breast cancer[J]. Lancet, 2017, 389(10074): 1134-1150.
[2] Bianchini G, Balko JM, Mayer IA, et al.Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease[J]. Nat Rev Clin Oncol, 2016, 13(11): 674-690.
[3] Kindts I, Buelens P, Laenen A, et al.Omitting radiation therapy in women with triple-negative breast cancer leads to worse breast cancer-specific survival[J]. Breast, 2017, 32: 18-25.
[4] Moran MS.Radiation therapy in the locoregional treatment of triple-negative breast cancer[J]. Lancet Oncol, 2015, 16(3): e113-122.
[5] Singletary SE, Connolly JL. Breast cancer staging: working with the sixth edition of the AJCC cancer staging manual[J]. CA Cancer J Clin, 2006, 56: 37-47
[6] 邓铁涛.中医证侯规范[S].广州:广东科学技术出版社,1990: 55.
[7] 陈锐深.现代中医肿瘤学[M].北京:人民卫生出版社, 2003: 401-419.
[8] Stovgaard ES, Nielsen D, Hogdall E, et al.Triple negative breast cancer - prognostic role of immune-related factors: a systematic review[J]. Acta Oncol, 2018, 57(1): 74-82.
[9] Sadelain M, Rivière I, Riddell S.Therapeutic T cell engineering[J].Nature, 2017, 545(7655): 423-431.
[10] 王晨,梁晨露,俞星飞,等.乳腺癌中医辨证分型联合分子分型预测新辅助化疗疗效的应用研究[J].中华中医药学刊,2017,35(2):283-286.
[11] 张耀,周敬,倪华栋.中西医结合治疗对于乳腺癌术后疗效及临床应用价值[J].中华中医药学刊,2017,35(11):2943-2945.
[12] Xia Y, Wang J, Li X. Apoptosis of human breast carcinoma MCF-7 cells induced by Chinese herbal Shenghe Powder and correlated with alterations in P53, Survivin, and BCL2[J]. Integr Med, 2008, 7(4): 24-27.
[13] Xia Y, Li Y, Wang J, et al. Bidirectional function of shenghe powder on repair of radiation-induced DNA damage in glioma and astrocyte[J]. Afr J Tradit Complement Altern Med, 2011, 8(2): 196-206.
[14] Wang J, Xia Y, Wang H, et al. Chinese herbs of Shenghe Powder reverse multidrug resistance of gastric carcinoma SGC-7901[J]. Integr Cancer Ther, 2007, 6(4): 400-404.
[15] Spitzer MH, Carmi Y, Reticker-Flynn NE, et al. Systemic immunity is required for effective cancer immunotherapy[J]. Cell, 2017, 168(3): 487-502.
[16] Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases[J]. Nat Rev Drug Discov, 2017, 16(3):203-222.
[17] Ito Y, Inoue A, Seers T, et al. Identification of targets of tumor suppressor microRNA-34a using a reporter library system[J]. Proc Natl Acad Sci U S A, 2017, 114(15):3927-3932
[18] Sun YX, Li H, Feng Q, et al. Dysregulated miR34a/diacylglycerol kinase ζ interaction enhances T-cell activation in acquired aplastic anemia[J]. Oncotarget, 2017, 8(4):6142-6154.
[19] 蒋晓月,江瑛.乳酸脱氢酶和Warburg效应的研究进展[J].生理科学进展, 2017, 48(5):352-356.
[20] Xiao X, Huang X, Ye F, et al. The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer[J]. Sci Rep, 2016, 6:21735.
[21] Buck MD, Sowell RT, Kaech SM, et al. Metabolic instruction of immunity[J]. Cell, 2017, 169(4):570-586.
[2] Bianchini G, Balko JM, Mayer IA, et al.Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease[J]. Nat Rev Clin Oncol, 2016, 13(11): 674-690.
[3] Kindts I, Buelens P, Laenen A, et al.Omitting radiation therapy in women with triple-negative breast cancer leads to worse breast cancer-specific survival[J]. Breast, 2017, 32: 18-25.
[4] Moran MS.Radiation therapy in the locoregional treatment of triple-negative breast cancer[J]. Lancet Oncol, 2015, 16(3): e113-122.
[5] Singletary SE, Connolly JL. Breast cancer staging: working with the sixth edition of the AJCC cancer staging manual[J]. CA Cancer J Clin, 2006, 56: 37-47
[6] 邓铁涛.中医证侯规范[S].广州:广东科学技术出版社,1990: 55.
[7] 陈锐深.现代中医肿瘤学[M].北京:人民卫生出版社, 2003: 401-419.
[8] Stovgaard ES, Nielsen D, Hogdall E, et al.Triple negative breast cancer - prognostic role of immune-related factors: a systematic review[J]. Acta Oncol, 2018, 57(1): 74-82.
[9] Sadelain M, Rivière I, Riddell S.Therapeutic T cell engineering[J].Nature, 2017, 545(7655): 423-431.
[10] 王晨,梁晨露,俞星飞,等.乳腺癌中医辨证分型联合分子分型预测新辅助化疗疗效的应用研究[J].中华中医药学刊,2017,35(2):283-286.
[11] 张耀,周敬,倪华栋.中西医结合治疗对于乳腺癌术后疗效及临床应用价值[J].中华中医药学刊,2017,35(11):2943-2945.
[12] Xia Y, Wang J, Li X. Apoptosis of human breast carcinoma MCF-7 cells induced by Chinese herbal Shenghe Powder and correlated with alterations in P53, Survivin, and BCL2[J]. Integr Med, 2008, 7(4): 24-27.
[13] Xia Y, Li Y, Wang J, et al. Bidirectional function of shenghe powder on repair of radiation-induced DNA damage in glioma and astrocyte[J]. Afr J Tradit Complement Altern Med, 2011, 8(2): 196-206.
[14] Wang J, Xia Y, Wang H, et al. Chinese herbs of Shenghe Powder reverse multidrug resistance of gastric carcinoma SGC-7901[J]. Integr Cancer Ther, 2007, 6(4): 400-404.
[15] Spitzer MH, Carmi Y, Reticker-Flynn NE, et al. Systemic immunity is required for effective cancer immunotherapy[J]. Cell, 2017, 168(3): 487-502.
[16] Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases[J]. Nat Rev Drug Discov, 2017, 16(3):203-222.
[17] Ito Y, Inoue A, Seers T, et al. Identification of targets of tumor suppressor microRNA-34a using a reporter library system[J]. Proc Natl Acad Sci U S A, 2017, 114(15):3927-3932
[18] Sun YX, Li H, Feng Q, et al. Dysregulated miR34a/diacylglycerol kinase ζ interaction enhances T-cell activation in acquired aplastic anemia[J]. Oncotarget, 2017, 8(4):6142-6154.
[19] 蒋晓月,江瑛.乳酸脱氢酶和Warburg效应的研究进展[J].生理科学进展, 2017, 48(5):352-356.
[20] Xiao X, Huang X, Ye F, et al. The miR-34a-LDHA axis regulates glucose metabolism and tumor growth in breast cancer[J]. Sci Rep, 2016, 6:21735.
[21] Buck MD, Sowell RT, Kaech SM, et al. Metabolic instruction of immunity[J]. Cell, 2017, 169(4):570-586.