中藥複方 T33 誘導自噬作用抑制 人類乳癌及腸癌細胞增生之研究

The Study of Traditional Chinese medicine formula T33 inhibits the proliferation of human breast cancer and colorectal cancer by inducing autophagy

劉育德(Yu-Te Liu)

指導教授 ： 徐再靜

中山醫學大學/醫學院/醫學研究所 (原生化微生物免疫研究所)/博士(2022年)

https://doi.org/10.6834/csmu202200081

摘要

癌症蟬聯 39 年來十大死因第一名，其中乳癌是台灣女性癌症第一位， 腸癌是台灣十大癌症死因第一位，兩種癌症在臨床治療上皆有困境。三 陰性乳癌因易復發、易轉移、預後差，過去治療採手術和化學治療，但 療效不佳。近年來雖有標靶藥物和免疫療法，但僅適用晚期或轉移型的 三陰性乳癌病人。而腸癌因早期症狀不明顯，往往確診時已經第二或第 三期，甚至到達晚期。腸癌晚期因標靶藥物產生抗藥性，造成療效不佳， 導致無藥可用的窘境。因此，本研究目的為探討中藥複方 T33 對乳癌及 腸癌細胞的影響機制。本研究利用細胞存活率試驗和細胞遷移檢測分析 中藥複方 T33 對乳癌 (MDA-MB231 和 MCF-7)，和腸癌 (HT-29 和 Caco 2) 細胞的增生和遷移影響。並使用免疫螢光染色和西方墨點法進行 自噬作用分析。最後利用裸鼠模式進行 T33 對活體療效評估。結果發現 中藥複方 T33 具有(1)降低乳癌和腸癌細胞增生及遷移的能力; (2)誘導細 胞自噬作用產生; (3)抑制腫瘤異種移植動物模式之癌細胞生長能力。綜合 上述研究結果顯示中藥複方 T33 對乳癌和腸癌細胞具有抑制增生、抑制 侵襲和誘導自噬之作用，並具有發展成為另一新抗癌藥物的潛力。

關鍵字

自噬 ； 乳癌 ； 腸癌 ； T33 ； 中藥

並列摘要

Cancer has been ranked first among the top ten causes of death for 39 years, among which breast cancer is the number one cancer among women in Taiwan, and colorectal cancer is the number one cause of death among the top ten cancers in Taiwan. Both cancers have difficulties in clinical treatment. Triple-negative breast cancer is prone to recurrence, metastasis, and poor prognosis. In the past, surgery and chemotherapy were used for treatment, but the efficacy was poor. Although there have been targeted drugs and immunotherapy in recent years, they are only suitable for patients with advanced or metastatic triple-negative breast cancer. Colon cancer is often diagnosed in the second or third stage, or even in the advanced stage, due to the lack of obvious symptoms in the early stage. In the advanced stage of colorectal cancer, drug resistance occurs due to target drugs, resulting in poor efficacy and the dilemma of no drugs available. Therefore, the purpose of this study was to investigate the effect of T33, a traditional Chinese medicine compound, on breast and colorectal cancer cells. In this study, cell viability and cell migration assay were used to analyze the effects of T33 on the proliferation and migration of breast cancer (MDA-MB231 and MCF-7), and colorectal cancer (HT-29 and Caco 2) cells. Autophagy analysis was performed using immunofluorescence staining and Western blotting. Finally, the efficacy of T33 in vivo was evaluated in nude mice. The results showed that T33 has the ability to (1) reduce the proliferation and migration of breast and intestinal cancer cells; (2) induce autophagy; (3) inhibit the growth of cancer cells in the tumor xenograft animal model. Based on the above research results, it is shown that the traditional Chinese medicine compound T33 has the effects of inhibiting proliferation and invasion and inducing autophagy in breast and colorectal cancer cells, and has the potential to develop into another new anticancer drug.

並列關鍵字

Autophagy ； breast cancer ； colorectal cancer ； T33 ； Traditional Chinese Medicine

參考文獻

1、 衛生福利部國民健康署•108 年癌症登記報告•取自: https://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=269 pid=14913

2、 衛生福利部統計處•109 年死因統計•取自: https://dep.mohw.gov.tw/dos/lp-5069-113-xCat-y109.html

3、 International Agency for Research on Cancer. Latest global cancer data: Cancer burden rises to 19.3 million new cases and 10.0 million cancer deaths in 2020. Retrieved from https://www.iarc.who.int/featured-news/latest-global-cancer-data-cancer- burden-rises-to-19-3-million-new-cases-and-10-0-million-cancer-deaths- in-2020/ (Dec. 31, 2021)

4、 Yip CH. Breast cancer in Asia. Methods Mol Biol. 2009; 471:51-64.

5、 Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the human development index (2008–2030): a population based study. Lancet Oncol. 2012; 13(8): 790-801.