Fig. 1

Hypoxic tumor cell-derived sEVs alleviate cell damage induced by IR and enhance radioresistance. A The expression of total protein in sEVs derived from hypoxic and normoxic CC cells was detected by BCA method. *P < 0.05 versus normoxic tumor cells. B Nano was used to detect the total RNA content in sEVs derived from hypoxic and normoxic tumor cells. **P < 0.01 versus normoxic tumor cells. C SiHa and Hela CC cells were co-cultured with PBS, NE-sEVs, HE-sEVs, tumor cell apoptosis was measured after 4 Gy radiation treatment by flow cytometry. D Expression of γ-H2AX protein in blank control cells, HE-sEVs or NE-sEVs-treated cells after 4 Gy radiation treatment was detected by Immunofluorometric assay. **P < 0.01 versus normoxic tumor cells with PBS. E Expression of γ-H2AX protein after different doses of HE-sEV treatment was detected by Immunofluorometric assay. *P < 0.05 and **P < 0.01 versus normoxic tumor cells with PBS. F The apoptotic cells treated with different doses of HE-sEVs in SiHa and Hela CC cells was detected and quantitatively analyzed by flow cytometry. *P < 0.05 and **P < 0.01 versus normoxic tumor cells with PBS. G The flow chart of animal study. H The tumor volume and weight in mice after different treatments with PBS + IR, NE-sEVs + IR, HE-sEVs + IR was measured (n = 6 in each treatment group). **P < 0.01 versus PBS + IR group and HE-sEVs + IR group. I The representative images of HE, Ki67 and TUNEL staining in PBS + IR, NE-sEVs + IR, HE-sEVs + IR groups. In HE, less damage is seen in HE-sEVs treatment; in Ki67 staining, brown indicates positive stating while blue indicates nuclear; in TUNEL staining, green indicates positive staining. Scale bar: 20 μm. All irradiation treatment was performed with a single 4 Gy. J Right panel shows the quantification of Ki67-positive and TUNEL-positive cells in PBS + IR, NE-sEVs + IR, HE-sEVs + IR groups. **P < 0.01 and ***P < 0.001 versus PBS + IR group and NE-sEVs + IR group