小GTPase Rab37對Formosanin C誘導之細胞自噬在肺癌細胞中的角色

Abstract

肺癌已經是台灣多年來死亡率第一名的癌症。轉移是治療肺癌最重要挑戰。中草藥重樓皂苷萃取物Formosanin C（FC）被發現可以藉由誘導降解型細胞自噬以及透過抑制組織金屬蛋白酶（MMPs）來降低肺癌轉移。降解型細胞自噬為細胞分解胞內物質以維持細胞能量平衡的方式。在肺癌細胞，人類小型GTPase Rab37增加金屬蛋白酶組織抑制劑（TIMP1）透過「分泌型細胞自噬」，降低MMP9的分泌以抑制肺癌轉移。本研究發現FC能夠（1）毒殺肺癌細胞CL1-5，（2）提高肺癌細胞的細胞自噬作用，其路徑與提高ATG7和Ras/MEK/ERK路徑的表現有關，（3）增加p62來抑制肺癌細胞的爬行。然而，在肺癌治療上，FC是否輔助化療藥物以發揮肺癌細胞致死的效果還有待更多證據釐清。Lung cancer has been the leading cause of cancer death in Taiwan for many years. Metastasis is a tricky challenge for lung cancer treatment. Formosanin C (FC), extracted from Chinese herbal saponin Rhizoma Paridis saponin (RPS), was found to have anti-tumor ability through inducing degradative autophagy and inhibiting pulmonary metastasis via repressing of matrix metalloproteinases (MMPs). Degradative autophagy degrades intracellular substances to maintain cell energy homeostasis. Human small GTPase Rab37 increases tissue inhibitor of metalloproteinase 1 (TIMP1) and reduces pulmonary metastasis through “secretory autophagy” in lung cancer cells. In the present studies, FC (1) inhibited CL1-5 lung cancer cell viability, (2) stimulated autophagy via upregulating ATG7 and Ras/MEK/ERK pathway, and (3) inhibited the cell migration through upregulating p62. However, whether FC can assist chemotherapy for lung cancer or not need much more research.