Macrophage‑derived exosomes attenuate the susceptibility of oral squamous cell carcinoma cells to chemotherapeutic drugs through the AKT/GSK‑3β pathway.

Abstract:

:Although chemotherapy is initially effective in debulking tumor mass in a number of different types of malignancy, tumor cells gradually acquire chemoresistance and frequently progress to advanced clinical stage. Accumulating evidence has indicated that the tumor sensitivity to several chemotherapeutic drugs is regulated by tumor stromal cells including macrophages. However, the role of macrophages in the efficacy of chemotherapeutics on oral squamous cell carcinoma (OSCC) cells is poorly understood. In the present study, the effects of macrophage‑secreted exosomes on the sensitivity of OSCC cells towards chemotherapeutic agents were examined. Specifically, the effects of exosomes derived from THP‑1 cells and primary human macrophages (PHM) were assessed on the chemosensitivity of OSC‑4 cells treated with 5‑fluorouracil (5‑FU) and cis‑diamminedichloroplatinum (CDDP). The THP‑1‑ and PHM‑derived exosomes promoted dose‑dependent proliferation, decreased the proliferative inhibitory effects of 5‑FU and CDDP and decreased apoptosis in OSC‑4 cells through activation of the AKT/glycogen synthase kinase‑3β signaling pathway. LY294002, a PI3K inhibitor, and MK‑2206, an AKT inhibitor, were both able to suppress the observed decrease in sensitivity to chemotherapeutic agents induced by exosomes. Overall, the data from the present study suggested that the macrophage‑derived exosomes may decrease the sensitivity to chemotherapeutic agents in OSCC cells. Thus, targeting the interaction between OSCC cells and macrophage‑derived exosomes may be considered as a therapeutic approach to improve the chemosensitivity of the tumor microenvironment in oral cancer.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Tomita R,Sasabe E,Tomomura A,Yamamoto T

doi

10.3892/or.2020.7748

subject

Has Abstract

pub_date

2020-11-01 00:00:00

pages

1905-1916

issue

5

eissn

1021-335X

issn

1791-2431

journal_volume

44

pub_type

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