以輔助療法口服多種氨基酸補充液增加小鼠肉瘤化學治療藥物效用的研究

Abstract

本研究探討了口服大豆衍生的多種氨基酸（MAA）對低劑量cyclophosphamide（CTX）的治療反應以及腫瘤負荷，細胞凋亡和自噬的潛在機制和作用。使用嚴重的聯合免疫缺陷（SCID）小鼠，並注射入肉瘤180（S-180）細胞。測量對肉瘤生長的反應，使用了3-甲基腺嘌呤(3-methyladenine)或Atg5的siRNA剔除 (siRNA knockdown)。將植入肉瘤細胞，CTX和口服鹽水的小鼠與植入肉瘤細胞，CTX和口服大豆衍生MAA補充劑的小鼠進行比較。結果顯示大豆衍生的MAA補充劑可顯著降低總體肉瘤負擔，增加caspase 3表現和Bax / Bcl-2比率，以及細胞凋亡，並降低LC3 II為媒介的自噬。用3-甲基腺嘌呤或Atg5 siRNA處理在上調(upregulating)細胞凋亡和下調(downregulating)細胞自噬方面，顯示與CTX加大豆衍生的MAA補充劑有類似的反應。低劑量的CTX結合口服大豆衍生的MAA補充劑經由上調細胞凋亡和下調細胞自噬具有強烈的抗腫瘤作用。

The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids’ oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis.