Umbilical cord blood mesenchymal stem cell-derived conditioned medium induces the apoptosis and autophagy of ovarian cancer SKOV3 cells

Q. Hua; L. Sun; HR. Li; HJ. Li; BD. Ma; YL. Wang

doi:10.54517/jbrha4471

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Umbilical cord blood mesenchymal stem cell-derived conditioned medium induces the apoptosis and autophagy of ovarian cancer SKOV3 cells

Q. Hua, L. Sun, HR. Li, HJ. Li, BD. Ma, YL. Wang

Article ID: 4471
Vol 35, Issue 5, 2021

DOI: https://doi.org/10.54517/jbrha4471

Received: 8 November 2021; Accepted: 8 November 2021; Available online: 8 November 2021; Issue release: 8 November 2021

Abstract

Mesenchymal stem cells (MSCs) are known to migrate to tumor tissues and play an important role in cancer progression. However, the effects of MSCs on tumor progression remain controversial. The aim of our study was to detect the effects of human umbilical cord blood-derived MSCs (hUCB-MSCs) on the human ovarian cancer SKOV3 cell line in vitro and the underlying mechanisms. MSCs were isolated from blood of umbilical vein in full-term healthy deliveries. SKOV3 cells were treated with conditioned medium (CM) from hUCB-MSCs. The CCK-8 (Cell Counting Kit) assay was used to determine the effect on proliferation. AnnexinV-FITC/PI staining was used to detect the cell cycle and apoptosis. Caspase-Glo®3/7 assay kit was used to detect the expression of caspase3/7 protein. Autophagy levels were determined based on expression of autophagic marker LC3, StubRFP-SensGFP-LC3 analysis, and electron microscopy. hUCB-MSCs are characteristically similar to other sources of MSCs, which are inconsistent with previous reports and exhibit multipotential differentiation capability (adipocytes and osteoblasts). The CCK-8 result revealed that hUCB-MSCs-CM inhibited the proliferation than those observed in the control group. Analysis of the cell cycle indicated that hUCB-MSCs-CM significantly increased the percentage of SKOV3 cells in the G2/M phase compared with the Ctrl group. Flow cytometry analysis and Caspase-Glo 3/7 Assay suggested that hUCB-MSCs-CM promoted apoptosis. hUCB-MSCs-CM increased LC3-II levels as well as autophagosome number in SKOV3 cells. These results indicate that hUCB-MSCs significantly inhibited the proliferation of SKOV3 cells in vitro, which is possibly due to blocking its cell cycle at G2/M phase and inducing SKOV3 cell death through synergistic apoptosis and autophagy. This theoretically supports hUCB-MSCs as an effective anticancer adjuvant in the treatment of ovarian cancer.

Keywords

umbilical cord blood mesenchymal stem cells;apoptosis;autophagy;cell cycle;ovarian cancer

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