六神丸联合化疗治疗中晚期胃癌的临床与诱导肿瘤细胞凋亡的实验研究
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摘要
目的:观察六神丸联合化疗治疗中晚期胃癌的疗效与通过体外细胞培养诱导高转移人肺腺癌A549细胞(简称人肺癌A549细胞)凋亡的作用,并探讨六神丸诱导人肺癌A549细胞凋亡的作用机理。方法:临床研究部分选取43例中晚期胃癌患者并随机分为观察组(化疗/OLF方案+六神丸组)和对照组(化疗组/OLF方案),其中观察组22例,对照组21例,均治疗2个疗程后比较两组治疗前后病灶大小、临床常见症状、体重、KPS评分、肿瘤标志物以及毒副作用的变化情况;体外细胞实验部分主要运用流式细胞仪、免疫组化法和RT-PCR技术观察六神丸诱导人肺癌A549细胞凋亡的作用及作用机理。结果:临床研究证实,六神丸具有显著改善肿瘤患者的临床症状和一般情况的作用,在控制肿瘤病灶方面,观察组有效率和病灶稳定率虽略高于对照组,但经统计学分析两组无显著性差异,在毒副作用方面也未见显著性差异;实验研究证实,六神丸具有诱导人肺癌A549细胞凋亡的作用,与顺铂联合应用有协同作用,并证实六神丸诱导人肺癌A549细胞凋亡的作用机理与上调Caspase-3的表达和下调Bcl-2、Survivin的表达有关。结论:六神丸可显著改善恶性肿瘤患者的临床症状,提高肿瘤患者的生存质量;六神丸可通过诱导肿瘤细胞凋亡发挥抗肿瘤作用,与顺铂联合应用产生协同作用。
Objective: The study observes“Liu-shen-wan”combined with chemotherapy curative effect to patients of advanced gastric cancer and the mechanism action of“Liu-shen-wan”inducing the apoptosis of human lung adenocarcinoma cell line A549.Methods: In the part of clinical study, 43 cases with advanced gastric cancers were randomly divided into two groups, 22 patients in the treated group were administered with“Liu-shen-wan”and chemotherapy (OXA+5-Fu+LV regimen), 21 in the control group with chemotherapy alone. Objective effects and the changes of clinical symptoms were studied after two periods of treatment. In part of vitro cell experiment, mainly use immunohistochemical staining,flow cytometric and RT-PCR technology to observe the mechanism of“Liu-shen-wan”inducing the apoptosis of human lung adenocarcinoma cell line A549. Results: Clinical research confirmed: tumor patients’clinical symptoms and quality of life were significantly improved in the treated group, better than in the control one. But there was no obvious difference between two groups on the size of focus and toxic and side-effect; Experimental study confirmed:“Liu-shen-wan”can induce the apoptosis of human lung adenocarcinoma cell line A549 by raising the level of Caspase-3 and reducing the level of Bcl-2 and Survivin, and combined with DDP can generate synergy. Conclusion:“Liu-shen-wan”can significantly improve tumor patients’clinical symptoms and enhance the quality of tumor patients’life;“Liu-shen-wan”can play antitumor effect by inducing tumor cell apoptosis approach, and combined with DDP can generate synergy.
Objective: The study observes“Liu-shen-wan”combined with chemotherapy curative effect to patients of advanced gastric cancer and the mechanism action of“Liu-shen-wan”inducing the apoptosis of human lung adenocarcinoma cell line A549.Methods: In the part of clinical study, 43 cases with advanced gastric cancers were randomly divided into two groups, 22 patients in the treated group were administered with“Liu-shen-wan”and chemotherapy (OXA+5-Fu+LV regimen), 21 in the control group with chemotherapy alone. Objective effects and the changes of clinical symptoms were studied after two periods of treatment. In part of vitro cell experiment, mainly use immunohistochemical staining,flow cytometric and RT-PCR technology to observe the mechanism of“Liu-shen-wan”inducing the apoptosis of human lung adenocarcinoma cell line A549. Results: Clinical research confirmed: tumor patients’clinical symptoms and quality of life were significantly improved in the treated group, better than in the control one. But there was no obvious difference between two groups on the size of focus and toxic and side-effect; Experimental study confirmed:“Liu-shen-wan”can induce the apoptosis of human lung adenocarcinoma cell line A549 by raising the level of Caspase-3 and reducing the level of Bcl-2 and Survivin, and combined with DDP can generate synergy. Conclusion:“Liu-shen-wan”can significantly improve tumor patients’clinical symptoms and enhance the quality of tumor patients’life;“Liu-shen-wan”can play antitumor effect by inducing tumor cell apoptosis approach, and combined with DDP can generate synergy.
引文
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[5]戴昕,李占全,冀林华.凋亡相关蛋白Caspase研究进展[J].中国现代医药杂志.2010,12(4):130-132.
[6] Roy S,Bayly CI,Gareau Y,et a1.Maintenance of caspase-3 proenzyme dormancy by an intrinsic‘safety catah’regulatory trieptide.Proc Natl Acad Sci USA,2001,98(11):6132-6137.
[7] Saikumar P,Dong Z,Mikhailov V,et a1.Apoptosis:definition,mechanism,and relevance to disease.Am JMed,1999,107(5):489-506.
[8] Poter AG,Janicke RU.Emerging roles of caspase-3 in apoptosis[J].Cell Death Diffe,1999,6(2):99-104.
[9] Reed Jc,Bcl-2 and the reculation of Programmed cell death.J Cell Biol,1994,124:I-2.
[10] Tsujimoto Y,Cossman J,Jaffe E,et a1.Involvement of the bc1-2 gene in human follicular lymphoma[J].Science,1985,228(4706):1440-1443.
[11] Korsmeyer SJ.Bcl-2 initiates a new category of oncogenes:reculator of cell death.Blood,1992,80:879.
[12] Leahy DT,Mulcahy HE,O’Donoghue DP,et al.Bc1-2 protein expression is associated with better prognosis in colorectal cancer [J].Histopathology,1999,35(4):360-367.
[13] Alsabeh R,Wilson CS,Ahn CW,et al.Expression of bc1-2 by breast cancer:A possible diagnostic application [J].Mod Pathol.1996,9(4):439-444.
[14] Oi-Long Lu,Richard Poulsom,Leslie Wong,et a1.Bcl-2 expression in adultand embryonic non-haematopoietic tissues.J Pathol,1993,169:431-432.
[15]王徽,宣兆燕,郑永晨.等.bcl-2基因在乳腺癌中的表达及临床意义[J].中
国癌症杂志.2001,11(3):252-256.
[16]于振刚,张居民,王炳辙.凋亡相关基因Bcl-2、Bax在NSCLC中的表达与细
胞凋亡的关系[J].临床肺科杂志.2010,15(1):13-15.
[17] Yin XM,Oltvai ZN,Korsmeyer SJ.BH1 and BH2 domains of Bc1-2 are required
for inhibition of apoptosis and heterodimerization with Bax [J].Nature,
1994,369(6478):321-323.
[18] Konopleva M,Tari AM,Estrov Z,et al.Liposemal Bcl-2 antisense
oligonucleotides enhance proliferation , sensitize acute myeloid
leukemia to cytosine-arabinoside,and induce apoptosis independent of
other antiapoptotic proteins [J].Blood.2000,95(12):3929-3938.
[19] Ambrosini G,Adida C,Altieri DC.A novel anti-apoptosis gene,survivin,
expressed in cancer and lymphoma[J].Nat Med,1997,3(8):917-921.
[20] Chantalat L,Skoufias DA,Kleman JP,et a1.Crystal structure of human
survivin reveals a bow tieshaped dimer with two unusual alphahelical
extensions [J].MolCell,2000,6(1):183-189.
[21] Fengzhi L,Ambrosini G,Chu EY,et a1.Control of apoptosis and mitotic
spindle by survivin.Nature,1998,396:580-588.
[22] Fukuda S,Pelus LM.Regulation of the inhibitor-0f-apoptosis family member
survivin in normal cord blood and bonemarrow CD34(+) cells by
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