RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Hyperthermia reduces cancer cell invasion and combats chemoresistance and immune evasion in human bladder cancer.
Hyperthermia reduces cancer cell invasion and combats chemoresistance and immune evasion in human bladder cancer.
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膀胱癌(BC)是一种常见的恶性肿瘤,其最常见的类型是尿路上皮癌,约占所有BC病例的~90%。目前BC的治疗选择有限,因此需要开发替代治疗策略。热疗(HT)作为一种辅助癌症治疗,已知可提高化疗或放疗的疗效。
本研究旨在探讨HT对人BC细胞系(5637、T24和UMUC3)中细胞存活、侵袭性、化疗耐药性和免疫逃逸的抗肿瘤作用。进行Calcein AM染色以分析HT处理后自然杀伤(NK)细胞对人BC细胞的细胞毒性。使用Transwell迁移和侵袭实验分析HT影响的细胞迁移和侵袭。发现HT通过下调蛋白激酶B的磷酸化抑制BC细胞的增殖。
此外,HT通过下调cadherin-11的表达,有效增强BC细胞对化疗药物顺铂(DDP)的敏感性并降低DDP耐药细胞的化疗耐药性。
进一步证明HT抑制BC细胞的迁移和侵袭并增强NK细胞的细胞毒性作用。总之,HT的抗肿瘤作用通过三种主要机制介导:增强BC细胞的化疗敏感性和减轻DDP诱导的化疗耐药性,抑制BC细胞的侵袭潜力并增强NK细胞的抗癌反应。因此,HT似乎是人类BC的一种有前景的辅助治疗。
Bladder cancer (BC) is a common malignancy and its most prevalent type is urothelial carcinoma, which accounts for ~90% of all cases of BC. The current treatment options for BC are limited, which necessitates the development of alternative treatment strategies. Hyperthermia (HT), as an adjuvant cancer therapy, is known to improve the efficacy of chemotherapy or radiotherapy.
The present study aimed to investigate the anti‑tumor effects of HT on cell survival, invasiveness, chemoresistance and immune evasion in human BC cell lines (5637, T24 and UMUC3). Calcein AM staining was performed to analyze the cytotoxicity of natural killer (NK) cells against human BC cells following HT treatment. Cell migration and invasion affected by HT were analyzed using Transwell migration and invasion assays. It was found that HT inhibited the proliferation of BC cells by downregulating the phosphorylation of protein kinase B.
Moreover, HT effectively enhanced the sensitivity of BC cells to the chemotherapy drug cisplatin (DDP) and reduced the chemoresistance of DDP‑resistant cells by downregulating the expression of cadherin‑11. It was further demonstrated that HT inhibited the migration and invasion of BC cells and enhanced the cytotoxic effects of NK cells.
In summary, the antineoplastic effects of HT were mediated through three main mechanisms: Enhancement of the chemosensitivity of BC cells and mitigation of DDP‑induced chemoresistance, suppression of the invasive potential of BC cells and reinforcement of the anticancer response of NK cells.
Thus, HT appears to be a promising adjunctive therapy for human BC.
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