Knockdown of MAGE‐A6 enhanced the irradiation sensitivity of non‐small cell lung cancer cells by activating the AMPK pathway

Abstract

Non-small cell lung cancer is a common respiratory tumor. The mortality rate of lung cancer patients has continued to rise in recent years. Several studies revealed that the expression of melanoma antigen 6 (MAGE-A6) promoted the development of multiple types of cancer. In addition, the suppression of AMPK pathway could restrict the radiosensitization of prostate cancer cells. Inhibition of MAGE-A6 activated the AMPK pathway in colorectal cancer cells. However, whether the MAGE-A6 could regulate the radiosensitivity of non-small cell lung cancer cells by regulating of the AMPK pathway is unclear. In this study, we established the MAGE-A6 knockdown in A549 and H1299 cells. Next, the apoptosis and proliferation of these cells were detected by the flow cytometry analysis and colony formation assay after the irradiation, respectively. Then, the expression of p-AMPKα1 and p-S6K1 in these cells was explored by the western blotting. After that, we inhibited the expression of AMPKα1 in MAGE-A6 knockdown cells. The proliferation and apoptosis of these cells were detected with colony formation assay and flow cytometry analysis. Finally, the tumor formation of these cells was detected in nude mice. Our results showed that inhibition of MAGE-A6 suppressed the proliferation and aggravated the apoptosis of A549 and H1299 cells after the irradiation. Knockdown of MAGE-A6 activated the expression of p-AMPKα1 and repressed the expression of p-S6K1 in these cells. Suppression of AMPKα1 in MAGE-A6 knockdown cells abolished these effects. Knockdown of MAGE-A6 also enhanced the radiosensitivity of these cells in vivo. These results suggested that inhibition of MAGE-A6 promoted the radiosensitivity of non-small cell lung cancer cells by activating AMPK pathway. Therefore, MAGE-6 has the potential to be explored as the therapeutic target for the treatment of non-small cell lung cancer in clinical.

Novel Long non-coding RNA MAGEA6-DT1 Promotes Expression of the Melanoma Antigen Family 6 by Demethylating its Enhancer

“…MAGE-A11 could promote the progression of esophageal cancer squamous cell carcinoma (ESCC) and cause poor prognosis [32]. Although some preliminary results about MAGE-A6 over-expression and its effect on cancer characteristics and treatment have been published [33,34], studies about speci c mechanism of MAGE-A6 expressing activation in solid tumor cells could be found scarcely.…”

Preclinical evidence using synthetic compounds and natural products indicates that AMPK represents a potential pharmacological target for the therapy of pulmonary diseases

“…131 MAGE-6 knockdownmediated activation of AMPK promoted the sensitiveness of A549 and H1299 cells to Gefitinib but AMPK knockdown inhibited the sensitiveness of A549 and H1299 cells to Gefitinib. 181 The activation of AMPK also contributed to the sensitivities of H1299 and A549 cells to the chemotherapy drugs Cisplatin and Doxorubicin and overcome the tumor resistance to Cisplatin in H1299 cells xenograft mouse model. 132 Chelidonine (a natural product) activated AMPK and inhibited the growth of H1975 cells in vitro and H1975 xenograft mice.…”

Phosphorylation of Bcl‐2 by JNK confers gemcitabine resistance in lung cancer cells by reducing autophagy‐mediated cell death

“…[17][18][19] JNK is also involved in autophagy-induced cell death. 20,21 According to previous reports, antitumor agents induce ACD by activating JNKmediated Beclin-1 expression. 22,23 The first known mammalian autophagy protein was called Beclin-1, a protein with only the BH3 domain.…”

“…Various stress factors can activate JNK, including oxidative stress or ultraviolet radiation 17–19 . JNK is also involved in autophagy‐induced cell death 20,21 . According to previous reports, antitumor agents induce ACD by activating JNK‐mediated Beclin‐1 expression 22,23 .…”