Vγ9Vδ2 T cells strengthen cisplatin inhibition activity against breast cancer MDA-MB-231 cells by disrupting mitochondrial function and cell ultrastructure

BackgroundBreast cancer ranks second of new cases and fifth of death in 2018 worldwide. Cis-platinum (CDDP) has been used as a chemotherapy to treat breast cancer for years. However, CDDP can adversely disrupt immune function of host. Thus, development of new protocol that can minimize side effect and meanwhile elevate clinical efficacy of CDDP will eventually benefit cancer patients. Since V gamma 9V delta 2 T cells can up-regulate immune function of cancer patients, therefore, our hypothesis is that introduction of V gamma 9V delta 2 T cells could potentiate CDDP efficacy against breast cancer.MethodsWe used breast cancer cell line MDA-MB-231 as model cell to test our hypothesis. The cancer cell viability in vitro in the context of different dose of CDDP was analyzed by flow cytometry. The cytoskeleton alteration was visualized by confocal microscopy, and the ultrastructure of cell membrane was observed by atomic force microscopy. The mitochondrial function of MDA-MB-231 cells was detected as well by flow cytometry.ResultsComparing to either V gamma 9V delta 2 T cells or CDDP alone, V gamma 9V delta 2 T cells plus CDDP could more strikingly induce MDA-MB-231 cell membrane ultrastructure disruption and cytoskeleton disorder, and more significantly enhance the inhibition of CDDP on proliferation of MDA-MB-231 cells. At the same time, V gamma 9V delta 2 T cells strengthened CDDP-induced mitochondrial dysfunction of cancer cells.ConclusionThis work revealed that V gamma 9V delta 2 T cells could synergistically enhance the inhibition activity of CDDP against breast cancer cells. Meanwhile, this in vitro proof-of-concept study implied the clinical prospect of the combining application of V gamma 9V delta 2 T cells and CDDP in breast cancer therapy.

Automated summary

The study found that introducing V gamma 9V delta 2 T cells can synergistically enhance the inhibitory activity of CDDP against breast cancer cells, producing more pronounced effects at the cellular level.