HC萃取物對癌細胞轉移及侵襲能力之影響

癌症在台灣及許多國家都是主要死因之一。雖然對於癌症治療的相關研究不斷在進行，直至今日仍尚未出現對轉移性癌症具效用的療法。針對轉移性癌症，化學治療是普遍常用的方式之一，但也常伴隨著副作用，如疲勞、噁心、嘔吐並且造成病患身體虛弱。因此針對此癌症開發具療效且低毒性的新藥物，有迫切性的需要。天然植物萃取物一般具低毒性且被使用於保健及草藥方面已有一段很長的時間。因此從天然植物萃取物找出有效成份作為治療癌症的輔助療法或者替代療法，是一種相當可行的方式。在台灣及中國，HC草藥常廣泛地被運用於抗病毒、抗菌、抗發炎及對抗癌症等方面。雖HC已被使用於抑制癌症病程，但其有效成分尚不清楚。在本篇研究中，我想釐清HC萃取物是否可抑制癌細胞的移動及侵襲能力，並且探討HC抑制癌細胞移動侵襲力的作用機制。與中研院農生中心蕭培文老師及生物技術開發中心賴宗賢、錢瑤珍老師合作，HC酒精萃取物經高效能液相層析法分離出不同部分。我的結果發現八號分離層(HC-8)能夠有效地抑制多種癌細胞的移動侵襲能力。這些癌細胞包括肺癌細胞(A549)、乳癌細胞(MDA-MB-231)、前列腺癌細胞(PC-3和CWR22Rv1)以及大腸癌細胞(KM12-SM)。有趣的是對正常前列腺表皮細胞(PNT2)，HC-8較不具影響力。在A549及PC-3細胞中，發現HC-8抑制癌細胞移動力，部份的原因是透過降低FAK、PDK1、AKT和mTOR的磷酸化，以及EGFR、HER2和mTOR蛋白質的量。另外經明膠酶譜法分析，發現HC-8可抑制A549和PC-3細胞分泌基質金屬蛋白酶二號(MMP2)及九號(MMP9)至胞外，進而降低其活性。總結以上的結果，HC-8能夠透過抑制EGFR、HER2、FAK、PDK1、AKT及細胞外MMP蛋白酶活性，進而有效地抑制癌細胞的侵襲移動能力。

關鍵字

中草藥；癌症；轉移；蛋白酶

並列摘要

Cancer has been the leading cause of death in Taiwan and around the world. Although many research works are trying hard to identify useful compounds or approaches for cancer therapy, there is currently no effective way to cure advanced human cancer. Chemotherapy is often used to treat cancer patients, but most chemotherapy has severe side effects and makes the patients painful and weakening. Therefore, to identify a new drug or compound with low toxicity and high efficacy is imperative for cancer therapy. Since botanical extracts or compounds contained in herbal medicine have been used for a long time and exhibit low toxicity, among them, HC herb has been wildly used in Taiwan and China as a medicine for antivirus, antibacteria, anti-cancer and anti-inflammation. Thus, in this study, I would like to identify whether HC herb ethanol extract have effective ingredients to inhibit human cancer cell migration and invasion, as well as what molecular mechanisms were affected by the effective HC extract. To isolate the effective fractions of HC, with collaborations with Drs. Pei-Wen Hsiao, Tzung-Hsein Lai and Yau-Jan Chyan, dry HC was used for ethanol extraction and the HC extracts were fractioned by HPLC. With cell migration and invasion assays, the results showed that the fraction 8 (HC-8) could effectually inhibit several cancer cell invasion and migration, including lung cancer (A549), breast cancer (MDA-MB-231), prostate cancer (PC-3, CW22Rv1) and colon cancer (KM12-SM) cells. Interestingly, HC-8 had no significant effect on the motility of normal prostate epithelial PNT2cells. Moreover, HC-8 to inhibit A549 and PC-3 cell motility was at least in part due to its effect on reducing the protein levels of EGFR, HER2 and mTOR, or the phosphorylation levels of FAK, PDK1, and AKT. In addition, we also found that HC-8 was able to reduce the zymographic activity of MMP2/9 by reducing the protease secretion in A549 and PC-3 cells. In conclusion, HC-8 can inhibit the migration and invasion of human cancer cells, at least partly due to their inhibitory effects on EGFR, HER2, FAK, PDK1 and AKT, as well as suppression of MMP proteolytic activity.

並列關鍵字

cancer ； invasion ； migration ； metastasis and MMP

參考文獻

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HC萃取物對癌細胞轉移及侵襲能力之影響

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