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.

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