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:Anticancer potential of Marina Crystal Minerals (MCM) against the growth of murine mammary adenocarcinoma cells in vivo.
Anticancer potential of Marina Crystal Minerals (MCM) against the growth of murine mammary adenocarcinoma cells in vivo.
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体外研究显示,Marina Crystal Minerals(MCM)是一种由海水矿物质和微量元素结晶形成的混合物,可在人体乳腺癌细胞MDA-MB-231中诱导凋亡并调节免疫。
本研究旨在评估MCM在体内对小鼠乳腺腺癌细胞的抗癌作用,并探究其机制。研究人员将Ehrlich腹水癌(EAC)细胞(一种乳腺腺癌)肌内接种小鼠,9天内可触及肿瘤。荷瘤小鼠自接种后第28天前,每周6天接受MCM腹腔内或瘤内注射,剂量40 mg/kg体重。研究评估肿瘤生长、细胞周期进展及调节蛋白、凋亡及其调节标志物、线粒体膜电位(MMP)、NK细胞活性和组织病理改变。MCM治疗使肿瘤体积在腹腔注射组降低49.4%,瘤内注射组降低59.5%。亚G1峰变化以及Annexin V/PI检测和组织病理学检查均证实MCM诱导癌细胞凋亡;其机制涉及Bax表达增加、caspase-3活化、Bcl-2表达降低及MMP破坏。
此外,MCM还诱导G1期细胞周期阻滞,表现为p53、p21和p27表达显著增加,癌细胞中cyclin D1和PCNA表达下降。
最后,MCM显著增强了NK细胞细胞毒活性。MCM具有化学预防潜力,可通过抑制细胞增殖、经线粒体依赖性通路诱导EAC细胞凋亡并激活免疫系统来降低肿瘤生长。结果提示MCM可能有益于乳腺腺癌治疗。
In vitro studies have shown that Marina Crystal Minerals (MCM), a crystallized mixture of minerals and trace elements from sea water, possesses apoptotic and immune modulatory effects in human breast cancer cells MDA-MB-231. The current study aimed to evaluate MCM's anticancer effect in vivo against murine mammary adenocarcinoma cells and to explore its underlying mechanisms. Mice were inoculated intramuscularly with Ehrlich ascites carcinoma (EAC) cells, a breast adenocarcinoma. Tumors became palpable within 9 days. Tumor-bearing mice were injected with MCM intraperitoneally (IP) or intratumorally (IT) at a dose of 40 mg/kg BW for 6 days/week until day 28 post-inoculation.
Tumor growth, cell cycle progression, cell cycle regulatory proteins, apoptosis, apoptotic regulatory markers, mitochondrial membrane potential (MMP), natural killer (NK) cell activity, and histopathological effects were investigated. Treatment with MCM reduced tumor volume by 49.
4% for IP and 59. 5% for IT injection. MCM induced cancer cell apoptosis, as indicated by a sub-G1 peak and confirmed by Annexin V/PI assay and histopathological examination. This was mediated by increased Bax expression, caspase-3 activation, decreased Bcl-2 expression, and MMP disruption.
Furthermore, MCM treatment induced G1 cell cycle arrest, mediated through significantly increased expression of p53, p21, and p27 and decreased expression of cyclin D1 and PCNA in cancer cells.
Finally, MCM treatment markedly enhanced NK cell cytotoxicity. MCM possesses chemopreventive potential to reduce tumor growth by suppressing cell proliferation, inducing apoptosis in EAC cells via a mitochondrial dependent pathway, and activating the immune system.
Our results suggest MCM's beneficial potential for treating breast adenocarcinoma.
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