嗜盐真菌多样性及其抗肿瘤活性研究

Study on the Biodiversity of Halophilic Fungi and Their Antitumor Activity

关键词:  嗜盐真菌  抗肿瘤  FGFR  海洋微生物  生物多样性

Key words:  halophilic fungi  antitumor  FGFR  marine microbe  biodiversity

摘要:

为探讨海盐田中的嗜盐真菌类型及其抗肿瘤作用，采用稀释涂布法和平板划线法分离海盐田中的可培养真菌，并基于ITS基因序列分析鉴定菌株，通过FGFR2过表达和未过表达的肿瘤细胞增殖抑制活性以及酶联免疫吸附法（Enzyme-Linked Immunosorbent Assay，ELISA）评价真菌的抗肿瘤作用。本研究分离得到11种嗜盐真菌，隶属于3科4属。真菌Epicoccum sorghinum（编号GXIMD02001）的提取物对FGFR2过表达的乳腺癌细胞MDA-MB-231-（S252W）增殖有较强的抑制作用，其半抑制浓度IC₅₀为11.02 μg/mL，而对FGFR2未过表达乳腺癌细胞MDA-MB-231几乎没有抑制活性，该提取物在1 mg/mL浓度下对FGFR2蛋白激酶活性抑制率为91.5%；两株真菌（编号GXIMD02004和GXIMD02009）对FGFR2表达乳腺癌细胞MDA-MB-231和MDA-MB-231（S252W）增殖抑制的IC₅₀为11.94-16.41 μg/mL；5株真菌的IC₅₀为219.2-449.7 μg/mL。嗜盐真菌（编号GXIMD02001）是首次报道具有靶向FGFR2抗肿瘤作用的海洋真菌，部分嗜盐真菌具有较好抗肿瘤作用，本研究为北部湾海洋微生物来源的抗肿瘤药物开发利用提供科学依据。

Abstract:

In order to investigate the types of halophilic fungi from the sea salt fields and their antitumor effects,the cultivable fungi in the sea salt fields were separated by the dilution coating and plate streaking methods,and the strain identification was carried out by the ITS gene sequence analysis.The anti-tumor effect of fungi was evaluated by FGFR2 over-expression of tumor cell proliferation inhibitory activity and Enzyme-Linked Immunosorbent Assay (ELISA).In this study,11 species of halophilic fungi were isolated and belonged to 3 families and 4 genera.The extracts of the fungus Epicoccum sorghinum(No.GXIMD02001) showed a strong anti-proliferative inhibitory effect on FGFR2 overexpressed breast cancer cells with an IC₅₀ of 11.02 μg/mL but had almost no inhibitory activity on FGFR2 breast cancer cell MDA-MB-231.The extracts of Epicoccum sorghinum (No.GXIMD02001) exhibited the inhibition rate of 91.5% against FGFR2 protein kinase at the concentration of 1 mg/mL.The IC₅₀ of the 2 fungi(No.GXIMD02004 and GXIMD02009) on the proliferation of FGFR2 breast cancer cells MDA-MB-231 and MDA-MB-231(S252W) was 11.94-16.41 μg/mL.The IC₅₀ of the 5 fungi is 219.2-449.7 μg/mL.It is concluded that the halophilic fungus (No.GXIMD02001) is the first marine fungus reported to have anti-tumor effects targeting the FGFR2.Parts of halophilic fungi exhibit good anti-tumor effect.This study provides scientific basis for the development and utilization of anti-tumor drugs from marine microbiological resources of Beibu Gulf.