Paclitaxel dose-dependent effect on the activity and level of NKG2D expression of NK cells isolated from breast cancer patients

Introduction: Paclitaxel is one of the most widely used chemotherapy drugs in the treatment of breast cancer. NK cell activation plays an important role in targeting tumor cells.

Objectives: In this study, we aimed to find doses of paclitaxel that, despite lethal effects on tumor cells, have the least side effects on NK cells, which are the first line of defense against tumor cells.

Methods: Blood samples were taken from breast cancer patients. NK cells were isolated using the Magnetic Activated Cell Sorting method, and co-cultured with SKBR-3 or MDA-MB-231 cells. These cells were treated with different doses of paclitaxel (0.15µM, 0.3µM, 0.6µM). Then, the amount of apoptosis was measured using the FITC-Annexin V. Then, the NKG2D expression was measured using real-time PCR, and the NK cytotoxicity was measured using AlamarBlue colorimetric assay.

Results: The expression of the NKG2D in NK cells treated with paclitaxel was significantly increased dose-dependently. On the other hand, the apoptosis induction in NK, MDA-MB-231, and SKBR-3 cells was augmented with increasing paclitaxel doses. The level of NK cytotoxicity against SKBR-3/MDA-MB-231 was increased in all doses, but the intensity of this activity was decreased dose-dependently, so that the cytotoxicity level was at its lowest at the dose 0.6µM.

Conclusion: According to the viability/apoptosis results, the 0.3µM paclitaxel dose left us with a higher percentage of active NK cells. Furthermore, the cytotoxicity against MDA-MB-231 and SKBR-3 was higher at the 0.3µM dose than at the 0.6µM dose, which is another confirmation of the preference to use the 0.3µM concentration and avoiding the 0.6µM dose.

These results indicate the need to adjust the dose used in chemotherapy based on the average cytotoxic effect on cancer cells and to support the immune system in fighting against tumor cells. Further study in this field helps to develop a better treatment protocol for cancer patients.

To be updated shortly..