Effects of Lactobacillus in Vaginal Radiotherapy for Gynecological Cancer

To explore the therapeutic effects of Lactobacillus delbrueckii subsp.lactis on radiation induced vaginal microbiota dysbiosis, vaginal radiation injury and the inhibitory effects of L.del on cervical cancer cells. Fifty-four gynecologic cancer patients (42 with cervical cancer and 12 with endometrial cancer) participated in the study. Twenty-six subjects received normal radiotherapy. Twenty-eight subjects received normal radiotherapy and L.del intervention. The vaginal swab samples were collected pre and post treatment and the vaginal microbiota was assessed by 16S rDNA sequencing. In vitro, the effects of L.del cytoplasmic on cervical cancer SiHa cells proliferation were analyzed with MTT and colony formation assay. Cell apoptosis was detected by Annexin V-FITC/PI staining. Radiotherapy resulted in vaginal microbiome dysbiosis characterized by increased phylogenetic diversity, decreased Lactobacillus and increased abundance of gram-negative non-fermenting bacteria. The occurrence of level 2 vaginal radiation injury is positively related to the abundance of Brevundimonas and gram-negative non-fermenting bacteria dominated in vagina. L.del administration could ameliorate vaginal microbiota dysbiosis and reduce the abundance of pathogens. In vitro, LDC inhibited SiHa cells proliferation through down-regulating the expression of BCL2, HPV16-E6, HPV16-E7, IL6 and MAP7, and up-regulating tumor suppressor genes BAX, Caspase-3, Caspase-9 and LTF. The conclusion is L.del application could alleviate the vaginal microbiome disorder caused by radiation therapy and restore the dominance of Lactobacillus in the vagina. In vitro, L.del cytoplasmic could inhibit the cell growth and promote the apoptosis in SiHa cells.