Paclitaxel Dose-Dependent Effect on the Activity and Level of NKG2D Expression of Natural Killer (NK) Cells Isolated from Breast Cancer Patients
| Author | Fateme Ghezelbash | en |
| Author | Mehdi Sheikhi | en |
| Author | Narges Baharifar | en |
| Author | Forough Chamaie Nejad | en |
| Author | Alireza Momeni | en |
| Author | Maedeh Almardan | en |
| Author | Arefeh Saeedian | en |
| Author | Amir Mashayekhi | en |
| Author | Nader Bagheri | en |
| Author | Myron R. Szewczuk | en |
| Author | Abdolkarim Sheikhi | en |
| Orcid | Abdolkarim Sheikhi [0000-0002-3559-5548] | en |
| Issued Date | 2025-06-30 | en |
| Abstract | Background: Paclitaxel is one of the most widely used chemotherapeutic agents for breast cancer treatment. Natural killer (NK) cells play an important role in targeting tumor cells. Objectives: This study aimed to identify paclitaxel doses that, while exerting lethal effects on tumor cells, cause the fewest side effects on NK cells, which constitute a first line of defense against tumor cells. Methods: NK cells from patients with breast cancer were isolated using the MACS method and co-cultured with SKBR-3/MDA-MB-231 cells. The cells were treated with different doses of paclitaxel (0.15 µM, 0.3 µM, and 0.6 µM). Apoptosis was assessed using FITC-Annexin V. Natural killer group 2, member D (NKG2D) expression was quantified using qPCR, and NK cytotoxicity was evaluated using the AlamarBlue colorimetric assay. Results: NKG2D expression in paclitaxel-treated NK cells increased significantly in a dose-dependent manner. In contrast, apoptosis in NK, MDA-MB-231, and SKBR-3 cells increased with increasing paclitaxel doses. NK cytotoxicity against SKBR-3 and MDA-MB-231 increased at all doses; however, the intensity of this activity decreased in a dose-dependent manner, and cytotoxicity was lowest at 0.6 µM paclitaxel. Based on the viability/apoptosis results, the 0.3 µM paclitaxel dose yielded a higher proportion of active NK cells. Moreover, cytotoxicity against MDA-MB-231 and SKBR-3 was higher at 0.3 µM than at 0.6 µM, further supporting the selection of 0.3 µM and avoidance of 0.6 µM. Conclusions: These results indicate the need to adjust chemotherapy dosing according to the average cytotoxic effects on cancer cells and to support the immune system. Further studies in this field may help to develop improved treatment protocols for patients with cancer. | en |
| DOI | https://doi.org/10.69107/jai-171655 | en |
| URI | https://brieflands.com/journals/jai/articles/171655 | en |
| Keyword | Paclitaxel | en |
| Keyword | Chemotherapy | en |
| Keyword | Natural Killer Cells | en |
| Keyword | NKG2D | en |
| Keyword | Breast Cancer | en |
| Publisher | Brieflands | en |
| Title | Paclitaxel Dose-Dependent Effect on the Activity and Level of NKG2D Expression of Natural Killer (NK) Cells Isolated from Breast Cancer Patients | en |
| Type | Research Article | en |
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