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  • 學位論文

松杉靈芝萃取物的抗癌研究 壹、松杉靈芝萃取物藉由停滯G2/M細胞週期而抑制大腸直腸癌細胞生長 貳、松杉靈芝萃取物藉由影響上皮細胞生長因子接受器表現及血管增生而抑制上皮癌細胞生長

Anticancer research on Ganoderma tsugae extracts I: Ganoderma tsugae extracts inhibit colorectal cancer cell growth via G2/M cell cycle arrest II: Ganoderma tsugae extracts inhibit expression of epidermal growth factor receptor and angiogenesis in human epidermoid carcinoma cells: In vitro and in vivo

指導教授 : 林松洲
共同指導教授 : 高銘欽(Ming-Ching Kao)
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摘要


靈芝素為亞洲國家用來治療各種疾病以及癌症的傳統生藥,本研究發現靈芝萃取物可造成大腸直腸癌細胞的生長週期停滯於細胞分裂期(G2/M phase)進而抑制癌細胞的生長,其作用機制可能是藉由減少細胞週期素 A與 B1以及增加週期素依賴激酶抑制蛋白 p21與 p27的表現量所致。在裸鼠腫瘤試驗結果顯示,靈芝萃取物可抑制腫瘤的生長,且經長時間投與並無明顯副作用產生,證實靈芝萃取物為一具有安全性的癌症治療藥物。另外,本研究在人類上皮癌 A-431細胞中證實具有抗血管增生的效果,不論在體外細胞或動物體內試驗,靈芝萃取物均可抑制細胞上皮生長因子接受器與血管內皮細胞生長因子的表現量,且能抑制人類臍帶靜脈內皮細胞類微血管管狀的形成;另外實驗也證明,藉由上皮生長因子的作用可以回復因靈芝萃取物的作用而受抑制的 VEGF表現量,所以證明靈芝萃取物可降低 VEGF的表現量是經由 EGFR的抑制而影響其下游訊息傳遞,繼而影響 VEGF在 A-431細胞的分泌及表現作用。本研究提供新的中草藥抗癌科學驗證,即靈芝萃取物可藉由細胞週期的停滯作用以及血管增生的影響作用而抑制腫瘤的生長,期待將來靈芝萃取物可進入臨床抗癌試驗,嘉惠更多癌症病人進行中草藥的治療。

並列摘要


Ganoderma, known as Lingzhi or Reishi, has been traditionally administered throughout Asian countries for centuries as cancer therapeutics and for other medicinal purposes. In this study, we find G. tsugae extracts (GTE) inhibit colorectal cancer cell proliferation caused by accumulating cells in G2/M phase, and it may be through downregulation of cyclin A and B1 and upregulation of p21 and p27. Tumorigenesis study in nude mice reveals the extracts cause tumor shrinkage. We also examine the anti-angiogenic effects of GTE on human epidermoid carcinoma A-431 cells. Our data indicate that GTE inhibits the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in vitro and in vivo, and also inhibits the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs). We also demonstrate that the suppression of VEGF expression by GTE can be restored by treatment with EGF. These results suggest that GTE inhibits VEGF expression via suppression of EGFR expression, resulting in the downregulation of VEGF secretion from epidermoid carcinoma A-431 cells. Therefore, these data provide new insights into the possible therapeutic use of G. tsugae for treating colorectal cancer and reveal a novel role for G. tsugae in inhibiting EGFR and VEGF expression, which are important for tumor angiogenesis and growth. This study provides molecular evidence that GTE exerts anti-tumor effects both in vitro and in vivo on colorectal adenocarcinoma and epidermoid carcinoma cells. Moreover, no significant physiological changes resulting from treatment with GTE on both colorectal cancer Colo205 and epidermoid carcinoma A-431 cells are observed in a safety assay using an animal model. Thus, G. tsugae may provide a potential therapeutic approach for anti-cancer treatment.

參考文獻


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