蓬莪术对卵巢癌 SKOV3 细胞的抗癌作用。
Anti-cancer effects of Kaempferia parviflora on ovarian cancer SKOV3 cells.
机构信息
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
Graduate School, Chiang Mai University, Chiang Mai, 50200, Thailand.
出版信息
BMC Complement Altern Med. 2018 Jun 11;18(1):178. doi: 10.1186/s12906-018-2241-6.
BACKGROUND
Kaempferia parviflora (KP) is an herb found in the north of Thailand and used as a folk medicine for improving vitality. Current reports have shown the anti-cancer activities of KP. However, the anti-cancer effects of KP on highly aggressive ovarian cancer have not been investigated. Therefore, we determined the effects of KP on cell proliferation, migration, and cell death in SKOV3 cells.
METHODS
Ovarian cancer cell line, SKOV3 was used to investigate the anti-cancer effect of KP extract. Cell viability, cell proliferation, MMP activity, cell migration, and invasion were measured by MTT assay, cell counting, gelatin zymography, wound healing assay, and Transwell migration and invasion assays, respectively. Cell death was determined by trypan blue exclusion test, AnnexinV/PI with flow cytometry, and nuclear staining. The level of ERK and AKT phosphorylation, and caspase-3, caspase-7, caspase-9 was investigated by western blot analysis.
RESULTS
KP extract was cytotoxic to SKOV3 cells when the concentration was increased, and this effect could still be observed even though EGF was present. Besides, the cell doubling time was significantly prolonged in the cells treated with KP. Moreover, KP strongly suppressed cell proliferation, cell migration and invasion. These consequences may be associated with the ability of KP in inhibiting the activity of MMP-2 and MMP-9 assayed by gelatin zymography. Moreover, KP at high concentrations could induce SKOV3 cell apoptosis demonstrated by AnnexinV/PI staining and flow cytometry. Consistently, nuclear labelling of cells treated with KP extract showed DNA fragmentation and deformity. The induction of caspase-3, caspase-7, and caspase-9 indicates that KP induces cell death through the intrinsic apoptotic pathway. The antitumor activities of KP might be regulated through PI3K/AKT and MAPK pathways since the phosphorylation of AKT and ERK1/2 was reduced.
CONCLUSIONS
The inhibitory effects of KP in cell proliferation, cell migration and invasion together with apoptotic cell death induction in SKOV3 cells suggest that KP has a potential to be a new candidate for ovarian cancer chemotherapeutic agent.
背景
Kaempferia parviflora（KP）是一种在泰国北部发现的草药，被用作提高活力的民间药物。目前的报告显示 KP 具有抗癌活性。然而，KP 对高度侵袭性卵巢癌的抗癌作用尚未得到研究。因此，我们确定了 KP 对 SKOV3 细胞增殖、迁移和细胞死亡的影响。
方法
使用卵巢癌细胞系 SKOV3 来研究 KP 提取物的抗癌作用。通过 MTT 测定、细胞计数、明胶酶谱、划痕愈合试验和 Transwell 迁移和侵袭试验分别测量细胞活力、细胞增殖、MMP 活性、细胞迁移和侵袭。通过台盼蓝排斥试验、AnnexinV/PI 与流式细胞术以及核染色来确定细胞死亡。通过 Western blot 分析研究 ERK 和 AKT 磷酸化以及 caspase-3、caspase-7、caspase-9 的水平。
结果
KP 提取物对 SKOV3 细胞具有细胞毒性，当浓度增加时，即使存在 EGF，这种作用仍然可以观察到。此外，用 KP 处理的细胞的细胞倍增时间明显延长。此外，KP 强烈抑制细胞增殖、细胞迁移和侵袭。这些结果可能与 KP 抑制明胶酶谱测定的 MMP-2 和 MMP-9 活性的能力有关。此外，KP 在高浓度时可诱导 SKOV3 细胞凋亡，通过 AnnexinV/PI 染色和流式细胞术证实。一致地，用 KP 提取物处理的细胞核标记显示 DNA 片段化和变形。caspase-3、caspase-7 和 caspase-9 的诱导表明 KP 通过内在凋亡途径诱导细胞死亡。KP 的抗肿瘤活性可能通过 PI3K/AKT 和 MAPK 途径调节，因为 AKT 和 ERK1/2 的磷酸化减少。
结论
KP 在 SKOV3 细胞中抑制细胞增殖、细胞迁移和侵袭以及诱导细胞凋亡的作用表明，KP 有可能成为卵巢癌化疗药物的新候选药物。
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