|
|
- 2015
得力生通过调节血管蛋白抑制肝癌SMMC-7721细胞增殖并促凋亡
|
Abstract:
摘要：目的 探讨得力生注射液对肝癌SMMC-7721细胞的作用机制。方法 用不同浓度的得力生作用肝癌SMMC-7721细胞后，MTT方法检测肝癌SMMC-7721细胞不同时间(24、48、72h)的增殖情况，流式细胞技术检测细胞凋亡及细胞周期，免疫细胞化学方法检测肝癌SMMC-7721细胞中血管内皮生长因子(vascular endothelial growth factor, VEGF)、骨桥蛋白(osteopontin, OPN)和内皮抑素(endostadin, ENS)的表达。结果 得力生作用于肝癌SMMC-7721细胞后，随着作用时间的延长和药物浓度的增加，细胞增殖逐渐减少，细胞凋亡逐渐增加，而对正常肝细胞HL-7702的作用很轻微。得力生将肝癌SMMC-7721细胞主要阻滞在G1期,且VEGF和OPN表达下调，ENS表达上调。结论 得力生抑制肝癌SMMC-7721细胞增殖及诱导凋亡，呈现时间和浓度依赖效应，并可能通过调节血管蛋白而实现，这为得力生治疗肝癌提供了理论依据。
ABSTRACT: Objective To investigate the possible anti-cancer mechanisms of Delisheng injection on hepatocellular carcinoma (HCC) cell line SMMC-7721. Methods Different concentration of Delisheng injection was administered on HCC cell line SMMC-7721. The cancer cell proliferation was measured by MTT assay. The apoptosis and cell cycle distribution were analyzed by flow cytometry. The expressions of vascular endothelial growth factor (VEGF), osteopontin (OPN) and endostadin (ENS) in SMMC7721 cells were detected by immunocytochemistry staining. Results Delisheng injection treatment resulted in a significant decrease in cell proliferation and induced apoptotic cell death with the increase of treatment time and drug concentration. Additionally, Delisheng inhibited the proliferation of HCC SMMC-7721 cells strongly and the viability of normal liver HL-7702 cells slightly. Delisheng primarily arrested SMMC-7721 cells at the G1 phase of the cell cycle. Immunocytochemistry staining showed that VEGF and OPN expressions were downregulated whereas ENS expression was upregulated. Conclusion Delisheng inhibits the proliferation of HCC SMMC-7721 cells and induces their apoptosis in dose- and time-dependent manners. This effect may be realized by regulating angiogenic proteins, which provides experimental evidence for the treatment of HCC with Delisheng
| [1] | EL-SERAG HB, MARRERO JA, RUDOLPH L, et al. Diagnosis and treatment of hepatocellular carcinoma[J]. Gastroenterol, 2008, 134(6):1752-1763. |
| [2] | WU P, DUGOUA JJ, EYAWO O, et al. Traditional Chinese medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis[J]. J Exp Clin Cancer Res, 2009, 28(1):112. |
| [3] | FANGHUA Q, ANYUAN L, LIN Z, et al. Cinobufacini, an aqueous extract from Bufo bufo gargarizans Cantor induces apoptosis through a mitochondria-mediated pathway in human hepatocellular carcinoma cells[J]. J Ethnopharmacol, 2010, 128(3):654-661. |
| [4] | TANAKA Y, FUJIWARA K, TANAKA H, et al. Paclitaxel inhibits expression of heat shock protein 27 in ovarian and uterine cancer cells[J]. Int J Gynecol Cancer, 2004, 14(4):616-620. |
| [5] | DENHARDT DT, GUO X. Osteopontin: a protein with diverse functions[J]. FASEB J, 1993, 7(15):1475-1482. |
| [6] | NYBERG P, XIE L, KALLURI R. Endogenous inhibitors of angiogenesis[J]. Cancer Res, 2005, 65(10):3967-3979. |
| [7] | O’REILLY MS, BOEHM T, SHING Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth[J]. Cell, 1997, 88(2):277-285. |
| [8] | THOMAS M. Molecular targeted therapy for hepatocellular carcinoma[J]. J Gastroenterol, 2009, 44(19):136-141. |
| [9] | PUROHIT A, HEJAZ HA, WALDEN L, et al. The effect of 2-methoxyoestrone-3-O-sulphamate on the growth of breast cancer cells and induced mammary tumours[J]. Int J Cancer, 2000, 85(4):584-589. |
| [10] | DENHARDT DT, NODA M, O’REGAN AW, et al. Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival[J]. J Clin Invest, 2001, 107(9):1055-1061. |
| [11] | SIEQEL RL, MILLER KD, JEMAL A. Cancer statistics, 2015 [J]. CA Cancer J Clin, 2015, 65(1):5-29. |
| [12] | LU CX, NAN KJ, NIE YL, et al. Delisheng, a Chinese medicinal compound, exerts anti-proliferative and pro-apoptotic effects on HepG2 cells through extrinsic and intrinsic pathways[J]. Mol Biol Rep, 2010, 37(7):3407-3412. |
| [13] | 孙海凤，阮之平，姚煜，等. 得力生注射液联合健择对肝癌HepG2细胞株增殖与凋亡的影响[J]. 现代肿瘤医学, 2013, 21(8):1716-1719. |
| [14] | KESSEL D, LUO Y. Cells in cryptophycin-induced cell-cycle arrest are susceptible to apoptosis[J]. Cancer Lett, 2000, 151(1):25-29. |
| [15] | HARAKEH S, ABU-EI-ARDAT K, DIAB-ASSAF M, et al. Epigallocatechin-3-gallate induces apoptosis and cell cycle arrest in HTLV-1-positive and negative leukemia cells[J]. Med Oncol, 2008, 25(1):30-39. |
| [16] | CARMELIET P, JAIN RK. Angiogenesis in cancer and other diseases[J]. Nature, 2000, 407(6801):249-257. |
| [17] | FERRARA N. Vascular endothelial growth factor: basic science and clinical progress[J]. Endocr Rev, 2004, 25(4):581-611. |
| [18] | DVORAK HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy[J]. J Clin Oncol, 2002, 20(21):4368-4380. |
| [19] | SHIJUBO N, UEDE T, KON S, et al. Vascular endothelial growth factor and osteopontin in tumor biology[J]. Crit Rev Oncog, 2000, 11(2):135-146. |
| [20] | 焦敏，南克俊，张茜，等. 华蟾素联合吉西他滨对肝癌HepG2细胞的抑制作用及对骨桥蛋白表达的影响[J]. 西安交通大学学报：医学版, 2010, 31(3):374-377. |
| [21] | REGE TA, FEARS CY, GLADSON CL. Endogenous inhibitors of angiogenesis in malignant gliomas: nature’s antiangiogenic therapy[J]. Neuro Oncol, 2005, 7(2):106-121. |
| [22] | SHI W, TESCHENDORF C, MUZYCZKA N, et al. Adeno-associated virus-mediated gene transfer of endostatin inhibits angiogenesis and tumor growth in vivo[J]. Cancer Gene Ther, 2002, 9(6):513-521. |
| [23] | WU SJ, CHANG SP, LIN DL, et al. Supercritical carbon extract of Physalis peruviana induced cell cycle arrest and apoptosis in human lung cancer H661 cells[J]. Food Chem Toxicol, 2009, 47(6):1132-1138. |
| [24] | QI FH, LI AY, INAGAKI Y, et al. Chinese herbal medicines as adjuvant treatment during chemo- or radio-therapy for cancer[J]. Biosci Trends, 2010, 4(6):297-307. |
| [25] | DOUGLAS H, JUDAH F. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis[J]. Cell, 1996, 86(3):353-364. |
| [26] | PAN XY, GUO H, HHAN J, et al. Ginsenoside Rg3 attenuates cell migration via inhibition of aquaporin 1 expression in PC-3M prostate cancer cells[J]. Eur J Pharmacol, 2012, 683(1-3):27-34. |
| [27] | ZHU ZT, LI EZ, LIU YY, et al. Inhibition of Jak-STAT3 pathway enhances bufalin-induced apoptosis in colon cancer SW620 cells[J]. World J Surg Oncol, 2012, 10:228. |
| [28] | ZHANG SW, ZHOU SY,SHAO JC, et al. Primary research on Chinese medicine treatment of androgen-independent prostate cancer[J]. Chin J Integr Med, 2009, 15(3):168-169. |
