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阿特珠单抗和 LncRNA PVT1 阻断协同通过 JAK2/STAT3/PD-L1 通路抑制顺铂耐药卵巢癌细胞的进展。

Atezolizumab and blockade of LncRNA PVT1 attenuate cisplatin resistant ovarian cancer cells progression synergistically via JAK2/STAT3/PD-L1 pathway.

机构信息

Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China; National Clinical Research Centre of Cancer, Tianjin 300060, China.

Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China; National Clinical Research Centre of Cancer, Tianjin 300060, China; Department of Cancer Prevention, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

出版信息

Clin Immunol. 2021 Jun;227:108728. doi: 10.1016/j.clim.2021.108728. Epub 2021 Apr 17.

Abstract

OBJECTIVE

To investigate the relationship between lncRNA PVT1(PVT1) level and PD-L1 expression and their functions in cisplatin resistant epithelial ovarian cancer (CREOC).

METHODS

PVT1 and PD-L1 in ovarian cancer tissues were detected and analyzed. The cells proliferation, apoptosis, invasion abilities and potential mechanism were detected by cell functional experiments and western-blot assay, respectively.

RESULTS

The average expressions of PVT1 and PD-L1 in CREOC tissues were significantly higher. The expression of PVT1 is positively associated with PD-L1 in CREOC. Higher expressions of PVT1 and PD-L1 indicated more malignant clinical behavior and shorter PFS and OS. Knockdown of PVT1 inhibited the proliferation and invasion and promote apoptosis for A2780cis cells, which may be related to decrease the expression of PD-L1 via repressing JAK2/STAT3 pathway.

CONCLUSIONS

The synergistic therapeutic strategy using LncRNA PVT1-targeted therapy and immune checkpoint blockade of PD-L1 warrant study further for ovarian cancer patients with cisplatin resistant recurrence.

摘要

目的

探讨长链非编码 RNA PVT1(PVT1)水平与 PD-L1 表达的关系及其在顺铂耐药上皮性卵巢癌(CREOC)中的作用。

方法

检测卵巢癌组织中 PVT1 和 PD-L1 的表达,并进行分析。通过细胞功能实验和 Western-blot 检测分别检测细胞增殖、凋亡、侵袭能力及其潜在机制。

结果

CREOC 组织中 PVT1 和 PD-L1 的平均表达均显著升高。在 CREOC 中,PVT1 的表达与 PD-L1 呈正相关。PVT1 和 PD-L1 表达较高表明更具恶性临床行为,PFS 和 OS 更短。敲低 PVT1 抑制 A2780cis 细胞的增殖和侵袭,促进凋亡,这可能与通过抑制 JAK2/STAT3 通路降低 PD-L1 的表达有关。

结论

针对 LncRNA PVT1 的靶向治疗与 PD-L1 免疫检查点阻断的协同治疗策略值得进一步研究,以用于顺铂耐药复发的卵巢癌患者。

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