研究动态
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弓形虫棒状蛋白16对肺腺癌细胞的抗癌机制。

The anticancer mechanisms of Toxoplasma gondii rhoptry protein 16 on lung adenocarcinoma cells.

发表日期:2024 Dec 31
作者: Guangqi Li, Qinhui Li, Yongqing Tong, Jin Zeng, Tiantian Dang, Ningai Yang, Yuning Zhou, Lei Ma, Qirui Ge, Zhijun Zhao
来源: Parasites & Vectors

摘要:

肺腺癌是肺癌最常见的亚型,是全世界癌症相关死亡的主要原因。弓形虫(T.gondii)棒状体蛋白16(ROP16)已被证明能快速进入细胞核,并通过磷酸化STAT3激活宿主细胞信号通路,并可能影响肿瘤细胞的存活。本研究构建弓形虫ROP16 I/II/III重组慢病毒表达载体,并稳定转染A549细胞,利用该载体探讨ROP16对A549细胞增殖、细胞周期、凋亡、侵袭和迁移的影响。 CCK-8、流式细胞术、qPCR、Western blotting、TUNEL、Transwell实验和细胞划痕实验均在来自患者术后癌组织的原发性人肺腺癌细胞中得到证实。 I型和III型ROP16激活STAT3并抑制A549细胞增殖,调节p21、CDK6、CyclinD1的表达,并诱导细胞周期停滞在G1期。 ROP16还调节Bax、Bcl-2、p53、cleaved-Caspase3和Caspase9,诱导细胞凋亡,并减少A549细胞的侵袭和迁移,而II型ROP16蛋白则无此作用。此外,在ROP16对原发性肺腺癌细胞的调节中,I型和III型ROP16表现出相同的抗癌潜力。这些发现证实了I型和III型ROP16的抗肺腺癌作用,为ROP16作为肺腺癌辅助治疗靶点的可能应用提供了新的视角,并推动精准治疗研究领域向肿瘤寄生虫治疗方向发展。
Lung adenocarcinoma is the most prevalent subtype of lung cancer, which is the leading cause of cancer-related mortality worldwide. Toxoplasma gondii (T.gondii) Rhoptry protein 16 (ROP16) has been shown to quickly enter the nucleus, and through activate host cell signaling pathways by phosphorylation STAT3 and may affect the survival of tumor cells. This study constructed recombinant lentiviral expression vector of T. gondii ROP16 I/II/III and stably transfected them into A549 cells, and the effects of ROP16 on cell proliferation, cell cycle, apoptosis, invasion, and migration of A549 cells were explored by utilizing CCK-8, flow cytometry, qPCR, Western blotting, TUNEL, Transwell assay, and cell scratch assay, and these effects were confirmed in the primary human lung adenocarcinoma cells from postoperative cancer tissues of patients. The type I and III ROP16 activate STAT3 and inhibited A549 cell proliferation, regulated the expression of p21, CDK6, CyclinD1, and induced cell cycle arrest at the G1 phase. ROP16 also regulated the Bax, Bcl-2, p53, cleaved-Caspase3, and Caspase9, inducing cell apoptosis, and reduced the invasion and migration of A549 cells, while type II ROP16 protein had no such effect. Furthermore, in the regulation of ROP16 on primary lung adenocarcinoma cells, type I and III ROP16 showed the same anticancer potential. These findings confirmed the anti-lung adenocarcinoma effect of type I and III ROP16, offering fresh perspectives on the possible application of ROP16 as a target with adjuvant therapy for lung adenocarcinoma and propelling the field of precision therapy research toward parasite treatment of tumors.