Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms22094974
Keywords
interleukin-32θ breast cancer; senescence; cell cycle arrest; drug resistance
Funding
- National Research Foundation of Korea (NRF) - Korean Government [2021R1A2C 3014577]
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IL-32θ exerts anti-proliferative effects in breast cancer cells, inducing permanent senescence and chromosomal instability, which may lead to resistance to doxorubicin (DR). Targeting IL-32θ in combination with DR treatment may not be suitable for treating metastatic breast cancer.
The recently discovered interleukin (IL)- 32 isoform IL-32 theta exerts anti-metastatic effects in the breast tumor microenvironment. However, the involvement of IL-32 theta in breast cancer cell proliferation is not yet fully understood; therefore, the current study aimed to determine how IL-32 theta affects cancer cell growth and evaluated the responses of IL-32 theta-expressing cells to other cancer therapy. We compared the functions of IL-32 theta in triple-negative breast cancer MDA-MB-231 cells that stably express IL-32 theta, with MDA-MB-231 cells transfected with a mock vector. Slower growth was observed in cells expressing IL-32 theta than in control cells, and changes were noted in nuclear morphology, mitotic division, and nucleolar size between the two groups of cells. Interleukin-32 theta significantly reduced the colony-forming ability of MDA-MB-231 cells and induced permanent cell cycle arrest at the G1 phase. Long-term IL-32 theta accumulation triggered permanent senescence and chromosomal instability in MDA-MB-231 cells. Genotoxic drug doxorubicin (DR) reduced the viability of MDA-MB-231 cells not expressing IL-32 theta more than in cells expressing IL-32 theta. Overall, these findings suggest that IL-32 theta exerts antiproliferative effects in breast cancer cells and initiates senescence, which may cause DR resistance. Therefore, targeting IL-32 theta in combination with DR treatment may not be suitable for treating metastatic breast cancer.
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