10P - Enriched gut microbiota increases anticancer drug efficacy in breast cancer cell lines: A promising in vitro approach

Background

Breast cancer is the most common and leading cause of cancer-related deaths in women. Recently, the gut-microbiome's dysbiosis has been noticed to impact on breast cancer and its management.Due to the adaptability of the variety of microbes and chemotherapeutic drugs used to treat breast cancer, mechanistic information is essential, yet these models are tedious and challenging to manage.

Methods

We have developed a unique setup to examine the relationship between gut microbiota and anticancer medications with breast cancer cell lines using IdMOC. The outside well contained MCF-7 and MDA-MB-231, and inner well contained a culture-enriched microbiome (CEM) obtained from pooled human faeces. Our designed setup allows free interaction of bacterial metabolites with the cell lines. Chemotherapeutic drugs like doxorubicin, paclitaxel, and carboplatin were added to the cells with variable concentrations of CEM from 100 to 1000 CFU at the inner well of the setup. Expression of Bcl-2, Bax and caspases-3, ras (oncogen), and MEK were measured in MCF-7 and MDA-MB-231 by quantitative PCR.

Results

Our research revealed that the response to anticancer drugs was in the following order: Doxorubicin > Paclitaxel > Carboplatin. These substances increased Bax and caspase-3 while down regulating the anti-apoptotic genes ras, MEK, and Bcl-2. It's interesting to note that these chemotherapeutic drugs had superior anticancer efficacy when they had a high titer of microbiome at least 1000 CFU. Particularly, when MCF-7 and MDA-MB-231 cells were grown with 1000 CFU of CEM instead of 100 CFU, Doxorubicin was 56% more effective at causing apoptosis, Paclitaxel was 40% more effective, and Carboplatin was 27% more effective.

Conclusions

We offer a novel method to evaluate the impact of anticancer medications while accounting for the function of gut bacteria. In this approach, traditional breast cancer cell lines are co-cultured with enriched microbiomes. According to the results of the current study, maintaining the natural microbiota improves the efficiency of cancer chemotherapy drugs. The microbiome should therefore be taken into consideration as a key factor for determining the pharmacology of anti-cancer medications.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Raktim Mukherjee, Vishnu Priya Veeraraghavan, Megha Dave, Selvaraj Jayaraman, A. Thirumal Raj, Shankargouda Patil.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.