Investigation of the Cytotoxic and Antiproliferative Effects of Liposomal Daunorubicin on Human Colorectal Cancer (HCT116) Cell Line

Abstract

Background: The incidence of colorectal cancer is increasing globally. Daunorubicin (DNR), an anthracycline antibiotic, is effective against various cancers. The PI3K/AKT/mTOR signaling pathway is crucial in regulating cell growth and cancer growth. Objectives: This study aims to evaluate the effects of liposomal daunorubicin (Lip-DNR) on cell proliferation and cell death induction in HCT116 cells compared to free daunorubicin. Methods: Lip-DNR was synthesized, and its shape and size were analyzed using FE-SEM imaging. HCT116 cells were treated with Lip-DNR concentrations of 0 (control), 0.125, 0.25, 0.5, 1, and 2 μm for 48 hours to determine the IC50. The effects of free (0.5 μm) and liposomal DNR (IC50 of 0.43 μm) on PI3K mRNA levels were assessed using real-time PCR. The cell cycle was analyzed by flow cytometry. Results: FE-SEM imaging showed that the liposomes are spherical and range from 50 - 100 nm in size. Lip-DNR induced cell death in HCT116 cells in a dose-dependent manner, with 0.5 μm Lip-DNR causing more cell death than an equivalent concentration of free DNR. Analysis of PI3K gene expression showed that DNR decreases PI3K gene transcription in HCT116 cells, with Lip-DNR having a more substantial effect than the free form. Both forms reduced the proportion of G2/M phase cells, but Lip-DNR was more effective at inhibiting cell proliferation in HCT116 cells. Conclusions: DNR inhibits the proliferation of HCT116 cells by downregulating PI3K gene expression and enhancing cell death, with the liposomal form demonstrating stronger effects than the free form.