Department of Oncology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Chin J Integr Med. 2011 Aug;17(8):607-11. doi: 10.1007/s11655-011-0815-y. Epub 2011 Aug 9.
To investigate the proliferation-inhibiting and apoptosis-inducing effects of ursolic acid (UA) and oleanolic acid (OA) on multi-drug resistance (MDR) cancer cells in vitro.
UA and OA in different concentrations (0-100 μmol/L) were added separately to cultures of different cancer cell lines, including the human colon cancer cell lines SW480 and SW620, human acute myelocytic leukemia cancer cell lines HL60 and HL60/ADR, human chronic myelogenous leukemia cell lines K562 and K562/ADR, and the human breast cancer cell lines MCF-7 and MCF-7/ADR. Effects of UA and OA on cell proliferation were detected by 3-(4,5-dimethyl-2-thiazole)-2-5-biphenly-tetrazole bromide (MTT) method and effects on cell apoptosis were tested by flow cytometry (FCM) and Western blot at 24, 48, and 72 h after treatment.
Both UA and OA showed significant inhibition on parent and MDR cell lines in a time- and concentration-dependent manner; the drug-resistant multiple of them on K562 and K562/ADR as well as on HL60 and HL60/ADR was 1; the effects of UA were better than those of OA in inhibiting cell growth of solid colonic cancer and breast cancer. After SW480 cells were treated by UA at the concentrations of 0-40 μmol/L for 48 h, FCM showed that annexin V (AV) positive cells and hypodiploid peak ratio increased along with the increase in the drug's concentrations; and Western blot found that expressions of Bcl-2, Bcl-xL and survivin decreased in a concentration-dependent manner.
Both UA and OA have antitumor effects on cancer cells with MDR, and the optimal effect is shown by UA on colonic cancer cells. Also, UA shows cell apoptosis-inducing effect on SW480, possibly by way of down-regulating the expressions of apoptosis antagonistic proteins, Bcl-2, Bcl-xL, and survivin.
研究熊果酸（UA）和齐墩果酸（OA）对体外多药耐药（MDR）癌细胞的增殖抑制和凋亡诱导作用。
分别向不同的癌细胞系培养物中加入不同浓度（0-100μmol/L）的 UA 和 OA，包括人结肠癌细胞系 SW480 和 SW620、人急性髓细胞白血病癌细胞系 HL60 和 HL60/ADR、人慢性髓细胞白血病癌细胞系 K562 和 K562/ADR 以及人乳腺癌细胞系 MCF-7 和 MCF-7/ADR。用 3-(4,5-二甲基-2-噻唑)-2,5-二苯基四氮唑溴盐（MTT）法检测 UA 和 OA 对细胞增殖的影响，并用流式细胞术（FCM）和 Western blot 在处理后 24、48 和 72 h 检测细胞凋亡的影响。
UA 和 OA 均表现出明显的抑制作用，呈时间和浓度依赖性，对 K562 和 K562/ADR 以及 HL60 和 HL60/ADR 的耐药倍数均为 1；UA 对实体结肠癌细胞和乳腺癌细胞的生长抑制作用优于 OA。SW480 细胞经 UA 处理浓度为 0-40μmol/L，作用 48 h 后，FCM 显示 Annexin V（AV）阳性细胞和亚二倍体峰比值随药物浓度的增加而增加；Western blot 发现 Bcl-2、Bcl-xL 和 survivin 的表达呈浓度依赖性降低。
UA 和 OA 对 MDR 癌细胞均有抗肿瘤作用，UA 对结肠癌细胞的作用最佳。此外，UA 对 SW480 细胞具有诱导细胞凋亡的作用，可能通过下调凋亡拮抗蛋白 Bcl-2、Bcl-xL 和 survivin 的表达。
