ArticleNeoplasia (New York, N.Y.)2018
Rapamycin Synergizes with Cisplatin in Antiendometrial Cancer Activation by Improving IL-27-Stimulated Cytotoxicity of NK Cells.
Article in Neoplasia (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- Natural killer cells at the interface of tumor immune escape and immunotherapy resistance in endometrial cancer.Frontiers in immunology · 2026Review
- Rapamycin inhibits tamoxifen-induced endometrial proliferation in vitro as a pilot approach for endometrial protection in breast cancer.Scientific reports · 2025Article
- Harnessing IL-27: challenges and potential in cancer immunotherapy.Clinical and experimental medicine · 2025Review
- Mitochondria-targeted strategies in tumor immunity.Frontiers in immunology · 2025Review
- The role and research progress of tumor-associated macrophages in cervical cancer.American journal of cancer research · 2024Review
- The Multifaceted Role of Autophagy in Endometrium Homeostasis and Disease.Reproductive sciences (Thousand Oaks, Calif.) · 2022Review
- The roles and clinical applications of interleukins in endometrial carcinoma.Frontiers in oncology · 2022Review
- An Overview of Autophagy inFrontiers in cellular and infection microbiology · 2022Review
- Insight of Autophagy in Spontaneous Miscarriage.International journal of biological sciences · 2022Review
- Autophagy in the physiological endometrium and cancer.Autophagy · 2021Review
- IL-12 Family Cytokines in Cancer and Immunotherapy.Cancers · 2021Review
- Delivery of Rapamycin by Liposomes Synergistically Enhances the Chemotherapy Effect of 5-Fluorouracil on Colorectal Cancer.International journal of nanomedicine · 2021Article
- The IFN-γ-IDO1-kynureine pathway-induced autophagy in cervical cancer cell promotes phagocytosis of macrophage.International journal of biological sciences · 2021Article
- The mechanism of and the association between interleukin-27 and chemotherapeutic drug sensitivity in lung cancer.Oncology letters · 2021Article
- CD1d expression and invariant natural killer T-cell numbers are reduced in patients with upper gastrointestinal cancers and are further impaired by commonly used chemotherapies.Cancer immunology, immunotherapy : CII · 2020Article
- The role of natural killer cells in hepatocellular carcinoma development and treatment: A narrative review.Translational oncology · 2019Review
- Downregulation of BAG3 attenuates cisplatin resistance by inhibiting autophagy in human epithelial ovarian cancer cells.Oncology letters · 2019Article
- CAGE-miR-140-5p-Wnt1 Axis Regulates Autophagic Flux, Tumorigenic Potential of Mouse Colon Cancer Cells and Cellular Interactions Mediated by Exosomes.Frontiers in oncology · 2019Article
- Role of Endometrial Autophagy in Physiological and Pathophysiological Processes.Journal of Cancer · 2019Review
- Autophagy Machinery as a Promising Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cell function is critical for controlling initial tumor growth and determining chemosensitivity of the tumor. A synergistic relationship between rapamycin and cisplatin in uterine endometrial cancer (UEC) in vitro has been reported, but the mechanism and the combined therapeutic strategy for endometrial cancer (EC) are still unknown. We found a positive correlation between the level of IL-27 and the differentiated stage of UEC. The increase of IL-27 in uterine endometrial cancer cell (UECC) lines (Ishikawa, RL95-2 and KLE) led to a high cytotoxic activity of NK cells to UECC in the co-culture system. Exposure with rapamycin enhanced the cytotoxicity of NK cells by upregulating the expression of IL-27 in UECC and IL-27 receptors (IL-27Rs: WSX-1 and gp130) on NK cells and further restricted the growth of UEC in Ishikawa-xenografted nude mice. In addition, treatment with rapamycin resulted in an increased autophagy level of UECC, and IL-27 enhanced this ability of rapamycin. Cisplatin-mediated NK cells' cytotoxic activity and anti-UEC activation were independent of IL-27; however, the combination of rapamycin and cisplatin led to a higher cytotoxic activity of NK cells, smaller UEC volume and longer survival rate in vivo. These results suggest that rapamycin and cisplatin synergistically activate the cytotoxicity of NK cells and inhibit the progression of UEC in both an IL-27-dependent and -independent manner. This provides a scientific basis for potential rapamycin-cisplatin combined therapeutic strategies targeted to UEC, especially for the patients with low differentiated stage or abnormally low level of IL-27.
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