Inhibitory Effect and Molecular Mechanism of the New Phorphyrin-Based HCE6 Photosensitizer on the Activity of MKN45 Human Gastric Cancer Cells

Gastric cancer is the fourth most common cancer worldwide and the third most common in Asia, with a high mortality. Photodynamic therapy (PDT) is a new treatment for cancer. With advantages of minimum invasiveness, small adverse side effects and high selectivity, PDT can be used as palliative treatment for patients with advanced gastric cancer. YLG I, also known as 2-(1 hexyloxyethyl)-2-devinyl porphin e6 trisodium salt (HCE6), is a recently developed photosensitizer. A previous study showed that HCE6 significantly inhibited the growth of QBC939 human cholangiocarcinoma cells. However, the effects and mechanisms of HCE6 on gastric cancer cell suppression are not known. In this study, we investigated the effects of HCE6 on the human gastric cancer cell line MKN45 and found that at the concentration of 2.0 mg/L, HCE6 almost completely killed MKN45 cells at a light intensity of 3.6 J/cm². RNAseq results confirmed that mitochondria and endoplasmic reticulum (ER)-mediated apoptosis was involved in the effects of HCE6 on cell death, and we also found that HCE6 induced chromosome conformational changes in the early phase of apoptosis. The results of our study help elucidate the molecular mechanisms underlying HCE6-mediated inhibition of gastric cancer cell growth and provide a theoretical basis and molecular targets for the treatment of gastric cancer.