Colorectal Cancer (CRC) therapy confronts challenges as chemoresistance and side effects. Therefore, drugs with antitumor properties that downmodulate aggressiveness mediators are required. Studies have shown the relevance of Low Molecular Weight Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B), and Transforming Growth Factor β (TGFβ) in mediating proliferation, chemoresistance, and metastasis. In this study, we aimed to investigate the responsiveness of colorectal cancer lines (HT29 and HCT116) towards Vemurafenib and whether this treatment could modulate these aggressiveness mediators. Cytotoxicity Assays (MTT and Trypan Exclusion Test) were performed to evaluate the viability of HT29 and HCT116 cells treated with Vemurafenib. Western blotting was performed to analyze the amount and/or the activity of mediators (LMWPTP, PTP1B, TGFβ, SMAD3), and the immunoprecipitation was performed to evaluate LMWPTP activity. This study brought up novel aspects of Vemurafenib action in colorectal cancer, which can decrease the activity of protein tyrosine phosphatases (LMWPTP and PTP1B) and the TGFβ pathway, making them important in the CRC aggressiveness. By downmodulating colorectal cancer hallmarks, Vemurafenib appears as an interesting candidate for CRC therapeutic protocols.

中文翻译：

---

威罗菲尼下调结直肠癌 (CRC) 的侵袭性介质：LMWPTP、PTP1B 和 TGFβ

结直肠癌 (CRC) 治疗面临着化疗耐药性和副作用等挑战。因此，需要具有下调侵袭性介质的抗肿瘤特性的药物。研究表明，低分子量酪氨酸磷酸酶 (LMWPTP)、蛋白酪氨酸磷酸酶 1B (PTP1B) 和转化生长因子 β (TGFβ) 在介导增殖、化学抗性和转移方面具有相关性。在这项研究中，我们旨在调查结直肠癌系（HT29 和 HCT116）对威罗菲尼的反应性，以及这种治疗是否可以调节这些侵袭性介质。进行细胞毒性试验（MTT 和锥虫排除试验）以评估用威罗菲尼处理的 HT29 和 HCT116 细胞的活力。进行蛋白质印迹以分析介质（LMWPTP，PTP1B、TGFβ、SMAD3)，并进行免疫沉淀以评估 LMWPTP 活性。这项研究提出了威罗菲尼在结直肠癌中作用的新方面，它可以降低蛋白酪氨酸磷酸酶（LMWPTP 和 PTP1B）和 TGFβ 通路的活性，使它们在 CRC 侵袭性中发挥重要作用。通过下调结直肠癌标志，威罗菲尼似乎是 CRC 治疗方案的一个有趣候选者。