Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 16 3 2026 09 30 Combination Therapy of Cisplatin and Naturally Induced Exosomes from Treated HeLa Cells: A Novel Drug-Free Strategy for Cervical Cancer Treatment 507 523 10.34172/apb.46428 EN Sanaz Aghajani https://orcid.org/0000-0001-8576-5990 Nasim Vousooghi Abbas Hajifathali Iman Seyhoun Javad Verdi https://orcid.org/0000-0003-0428-8323 Journal Article 10.34172/apb.46428 2025 09 22 2026 05 07 Introduction: Cisplatin and several other chemotherapeutic agents remain central to the treatment of cervical cancer, yet their therapeutic benefits are frequently constrained by significant systemic toxicity. Exosomes—small extracellular vesicles released by various cell types—are increasingly examined as potential carriers for drug delivery. Despite this interest, it is still not well understood whether these vesicles can independently propagate the biological effects triggered by a drug, even when the drug itself is no longer present. In this study, we explored whether exosomes collected from cisplatin treated HeLa cells could transfer apoptotic signals to untreated HeLa cells, a phenomenon we refer to as "Effect Delivery." Methods: Exosomes released by cisplatin treated HeLa cells were isolated through ultracentrifugation and subsequently characterized using standard analytical methods. To determine the appropriate working concentration, the cytotoxic impact of these exosomes on recipient cells was examined through the MTT assay. The ability of the exosomes to trigger apoptosis was then evaluated using flow cytometry, along with quantitative real time PCR (qRT PCR) to measure changes in the expression of key apoptosis related genes. Results: Exosomes isolated from cisplatin treated HeLa cells were found to induce apoptosis in 57.6% of recipient HeLa cells. This response was accompanied by upregulation of pro apoptotic genes, including BAX, Caspase 3, TP53, and TNF α, along with downregulation of antiapoptotic genes such as BCL2 and BIRC5. Notably, this pro apoptotic effect appeared to be selective for malignant cells, as no comparable apoptotic response was detected in noncancerous HEK293 cells. Conclusion: Our findings indicate that exosomes released from drug treated cancer cells can convey apoptotic signals to neighboring malignant cells, even in the absence of direct drug transfer. This observation points to a possible drug independent approach for amplifying antitumor responses and offers new perspectives on the role of exosome mediated communication in cancer therapy.