Radiotherapy plays an important part in the management of lung cancer . However, partial lung cancer cell’s resistance to radiotherapy affects therapeutic effects, and 5-year survival rate of radiotherapy alone is only 5%–10%, local recurrence occurs in 80% of patients, and metastasis occurs in 60% of patients . Therefore, it is necessary to find a effective radiosensitizer to enhance tumor radiosensitivity, while with less negtive function to normal tissues.
Myricetin, a nontoxic dietary flavonoid, could be easily found in many natural foods and medicinal herbs [26, 27]. Reports indicate that myricetin does not cause tumor formation in mice and attenuates the number of diol-epoxide-induced pulmonary tumors per mouse . It inhibits polycyclic aromatic hydrocarbon metabolism and subsequent polycyclic aromatic hydrocarbon–DNA adduct formation in lung . And many studies have shown that myricetin has antioxidant, anti-inflammatory and potent anticancer effects [15–18]. Therefore it was reasonable to hypothesize that myricetin might function as a radiosensitizer.
To test this hypothesis, we firstly conducted colony formation assays and prolifetation assay in lung cell lines (A549 and H1299), It was found that treatment of the cells with radiotherapy combined with myricetin could significantly decrease the surviving fraction and prolifetation of cancer cells. And in this study, we aslo engaged lung tumor bearing nude mice model to observe the radiosensitizing effect of myricetin in vivo. The result showed the tumor growth speed was significantly slower down in occurred for irradiated mice treated with myricetin. These data above demonstrate that myricetin has a radiosensitization potential in vitro and in vivo, and further indicated that myricetin can function as a powerful radiosensitizer for lung cancer.
Apoptosis is an important effect in the use of radiation to kill tumor cells, and it is now widely recognized that radiation-induced apoptosis may be used to measure the sensitivity of cells to radiation, with an increased rate of apoptosis meaning that the cells have a higher sensitivity to radiation [30–35]. In order to investigate the apoptosis effect of myricetin-induced radiosensitization, the apoptosis rate of A549 and H1299 cells were measured through FCM. The results showed that myricetin enhanced the radiosensitivity of apoptosis rate in lung cancer cells. And to further test the radiosensitizing effect of myricetin on tumor cells apoptosis, we detected the expression level of Caspase-3, which was plays a very important role during cells apoptosis. The data showed that myricetin could increase the expression of Caspase-3 in occurred for radiotherapy, which aslo indicated that myricetin could enhanced the radiosensitivity of apoptosis.
In conclusion, the results of the current study demonstrate the effect of myricetin on combination with radiotherapy enhances lung tumor radiosensitivity in vitro and in vivo, it could provied a novel insight into myricetin as a safe and potential agent for lung cancer radiosensitizers to enhance the effectiveness of radiotherapy.