Combination therapy of cisplatin and naturally induced exosomes from treated HeLa cells: A novel drug-free strategy for cervical cancer treatment

Abstract

Purpose: Cisplatin and other chemotherapy medications are widely used against cervical cancer, although their therapeutic benefits are sometimes constrained by systemic toxicity. Though mostly studied as drug carriers, exosomes—small vesicles secreted by cells—have yet to be shown to independently carry drug-induced effects. Here, we investigated whether exosomes from cisplatin-treated HeLa cells could trigger apoptosis in untreated HeLa cells through a mechanism we term “Effect Delivery,” without carrying the drug itself. Methods: Through ultracentrifugation from cisplatin-treated HeLa cells, exosomes were extracted and examined using a range of techniques. Using the MTT assay, the best dosage of exosomes generated from the treated HeLa cells needed to trigger apoptosis was found. Flow cytometry and qRT-PCR were used to determine the levels of apoptosis. Results: Results indicated that 57.6% of recipient HeLa cells experienced apoptosis induced by these exosomes, together with elevated expression of BAX, Caspase-3, TP53, and TNF-α, as well as reduced BCL2 and BIRC5 levels. Notably, the effect was selective for cancerous cells and did not affect non-cancerous HEK293 cells. Conclusion: Our results show that exosomes from drug-treated cancer cells may, independent of the drug itself, transmit apoptotic messages to other cancer cells. This finding points to a fresh, drug-free, and maybe safer technique for targeted cancer treatment.

Keywords: Cervical Cancer, Apoptosis, Exosome, Targeted Therapy, Effect Delivery, Exosome Delivery