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Published on: November 28, 2019
OK-432 Suppresses Proliferation and Metastasis by Tumor Associated Macrophages in Bladder Cancer
Yuan-Feng Tian1, Kun Tang, Wei Guan
1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Abstract:
OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer.
Insights
OK-432, a Streptococcus-derived immunotherapy, effectively inhibits bladder cancer cell proliferation and metastasis. It works by activating tumor-associated macrophages (TAMs) to release cytokines, offering a promising therapeutic strategy for bladder cancer.
Area of Science:
- Immunotherapy
- Oncology
- Cell Biology
Background:
- OK-432, a Streptococcus-derived immunotherapeutic, has a history of clinical success in various cancers.
- Tumor-associated macrophages (TAMs) play a crucial role in cancer progression and immune evasion.
Purpose of the Study:
- To investigate the anticancer effects of OK-432 on bladder cancer, focusing on its interaction with TAMs.
- To elucidate the mechanisms by which OK-432 impacts bladder cancer cell behavior and tumor growth.
Main Methods:
- MTS assay to assess cell proliferation in T24 and EJ bladder cancer cell lines.
- In vitro apoptosis induction assays.
- Analysis of epithelial-mesenchymal transition (EMT)-related factors.
- In vivo studies using a Sprague-Dawley (SD) rat model to evaluate tumor growth and metastasis, including Proliferating Cell Nuclear Antigen (PCNA) expression.
Main Results:
- OK-432 significantly inhibited proliferation and induced apoptosis in bladder cancer cells in vitro.
- OK-432 suppressed bladder cancer cell migration and invasion by modulating EMT-related factors.
- In vivo, OK-432 demonstrated inhibition of tumor growth, reduced PCNA expression, and suppressed metastasis.
Conclusions:
- OK-432 exhibits potent anticancer effects against bladder cancer.
- The mechanism involves the activation of TAMs, leading to cytokine secretion that inhibits cancer cell proliferation and metastasis.
- OK-432 represents a promising immunotherapeutic agent for bladder cancer treatment.
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