Radiation Nonclinical Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.
Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seongbuk-gu, Seoul 136-701, Korea.
Int J Mol Sci. 2020 Jan 29;21(3):871. doi: 10.3390/ijms21030871.
The tropical basidiomycete fungus Phellinus linteus (Mesima) exhibits anti-tumor, anti-angiogenic, and immunomodulatory properties in various cancers including prostate, colon, and lung cancer along with melanoma by, for example, inducing apoptosis or cell cycle arrest. However, whether medina also facilitates treatment of hepatocellular carcinoma (HCC), the third global cause of cancer deaths, remains unknown. Here, we examined its potential as a radiosensitizer in HCC radiotherapy using human HCC Hep3B and HepG2 cell lines and xenograft tumors. Mesima pretreatment significantly enhanced HCC cell radiosensitivity in vitro and the combination of mesima + radiation treatment significantly reduced xenograft tumor growth and size in vivo compared to those with single treatments. Mechanistically, mesima significantly enhanced radiotherapy efficiency by inhibiting tumor cell survival through inducing apoptosis (assessed via annexin V), impairing cell cycle regulation (shown by flow cytometry), and reducing radiation-induced DNA damage repair (measured via γ-H2AX foci). Combination treatment also facilitated autophagic cell death beyond that from single treatments (assessed by quantifying stained acidic vesicular organelles), and diminished tumor cell metastatic potentials (shown by wound and Transwell assays). These findings support the synergistic anti-tumor effects of mesima combined with radiation and suggest scientific evidence for mesima as a radiosensitizer in HCC.
热带担子菌真菌木蹄层孔菌（Mesima）通过诱导细胞凋亡或细胞周期阻滞等方式，在包括前列腺癌、结肠癌和肺癌以及黑色素瘤在内的多种癌症中具有抗肿瘤、抗血管生成和免疫调节特性。然而，木蹄层孔菌是否有助于治疗全球癌症死亡的第三大原因——肝细胞癌（HCC），目前尚不清楚。在这里，我们使用人肝癌 Hep3B 和 HepG2 细胞系和异种移植瘤研究了其作为 HCC 放射治疗增敏剂的潜力。Mesima 预处理可显著增强 HCC 细胞在体外的放射敏感性，与单一治疗相比，Mesima+放射治疗联合治疗可显著降低异种移植瘤的生长和大小。在机制上，Mesima 通过诱导细胞凋亡（通过 Annexin V 评估）、破坏细胞周期调节（通过流式细胞术显示）和减少放射诱导的 DNA 损伤修复（通过 γ-H2AX 焦点测量），显著提高了放射治疗效率，从而抑制肿瘤细胞的存活。联合治疗还促进了自噬性细胞死亡，超过了单一治疗的作用（通过定量染色的酸性液泡细胞器评估），并降低了肿瘤细胞的转移潜力（通过划痕和 Transwell 测定显示）。这些发现支持了 Mesima 与放射治疗联合的协同抗肿瘤作用，并为 Mesima 作为 HCC 放射增敏剂提供了科学证据。
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