BMI1 Silencing Liposomes Suppress Postradiotherapy Cancer Stemness against Radioresistant Hepatocellular Carcinoma

Radiotherapy causes DNA damage by direct ionization and indirect generation of reactive oxygen species (ROS) thereby destroying cancer cells. However, ionizing radiation (IR) unexpectedly elicits metastasis and invasion of cancer cells by inducing cancer stem cells' (CSCs) properties. As BMI1 is a crucial gene that causes radioresistance and an unfavorable prognosis of hepatocellular carcinoma (HCC), BMI1 inhibitor PTC-209 has been encapsulated in a ROS-responsive liposome (LP(PTC-209)) to be temporally and spatially delivered to radioresistant HCC tissue. The ROS generated during IR was not only considered to directly cause tumor cell death but also be used as a stimulator to trigger ROS-responsive drug release from LP(PTC-209). The PTC-209 released into resistant HCC tissue under radiotherapy further led to cancer stem cell (CSC) differentiation and then recovered radiosensitivity of HCC tumor. The suppression of the radioresistant performance of LP(PTC-209) has been proved on radiosensitive and radioresistant Hepa1-6 CSC tumor models, respectively. Our study clarified the relationship between radiotherapy and cancer stemness and provided insights to achieve complete suppression of radioresistant HCC tumor by inhibiting cancer stemness.

Automated summary

Radiotherapy can cause DNA damage and destroy cancer cells, but it can also induce cancer stem cell properties, leading to metastasis and invasion. Researchers have developed a ROS-responsive liposome containing the BMI1 inhibitor PTC-209 to target radioresistant HCC tissue. The study found that the released PTC-209 can restore radiosensitivity in HCC tumors by differentiating cancer stem cells.