利用藥物載體延後抑制乙型轉化生長因子對乳癌轉移的影響

Abstract

乳癌是在世界各國都很常見的一種癌症。治療乳癌的主要方式是透過手術切除腫瘤，但部分患者可能會面臨術後復發的問題，這對病人來說是一大威脅。而手術造成的傷口會改變改變周圍組織，形成如腫瘤微環境（TME）般，可以促進腫瘤發展的環境。因此，可以促進組織修復的物質，可能也有助於腫瘤復發，無論是在原位或遠端。乙型轉化生長因子（TGFβ）是關鍵的細胞因子，在多種傷口癒合，以及腫瘤發展的過程中發揮作用。本研究探討了利用藥物釋放平台裝載並在特定時間釋放乙型轉化生長因子抑制劑（TGFβ inhibitor）是否能減少復發。在進行體內研究前，我們先將纖維母細胞（3T3-L1）與乳腺癌細胞（4T1）共同培養，試圖模擬一個簡易的腫瘤微環境。再將乳腺癌細胞注射到小鼠乳腺腺體，以建立復發模型。手術過程中，我們在切除部位應用了含或不含乙型轉化生長因子抑制劑的脈衝式藥物釋放平台。結果顯示，接受乙型轉化生長因子抑制劑治療的小鼠，其肝臟和肺部的轉移病灶明顯減少，且纖維化區域亦較小。因此，這種藥物釋放系統可能是減少遠端復發（轉移）的潛在治療方法，值得進一步研究。

Breast cancer is a global health concern where surgery is the primary treatment, yet post-surgery recurrence remains a significant threat. Surgical wounds create an environment. This is reported to be similar to the tumor microenvironment (TME), potentially promoting tumor growth. Transforming growth factor β (TGFβ) is a pivotal cytokine participates in wound healing, which also influences tumor recurrence, no matter local or distant recurrence (metastasis). This study explores the potential of utilization of a drug-releasing platform to reduce recurrence. Prior to in vivo experiments, co-cultured fibroblasts (3T3-L1) and breast cancer cells (4T1) simulated a simplified TME. Mice models injected with these cells demonstrated reduced metastasis and fibrotic areas when treated with a TGFβ inhibitor embedded in a hydrogel during surgery. This approach shows promise in mitigating distant recurrence (metastasis), warranting further investigation.