Abstract
Objective This study aims to investigate the effect of heat shock protein-70 (Hsp70) on epithelial-mesenchymal transition (EMT) of lung cancer cells under heat stimulation and to explore its possible molecular mechanism. Methods qRT-PCR and immunohistochemistry assay were used to detect the expression of Hsp70 in lung cancer tissues and adjacent tissues. EdU assay was used to detect the cell activity. The effect of Hsp70 on the migration and invasion of A549 and NCI-H446 cells was detected by the wound-healing assay and Transwell assay. A tumor transplantation animal model was established to detect the effect of overexpression of Hsp70 on proliferation and metastasis of lung cancer cells. Western blot assay was used to detect the effect of thermal stimulation and overexpression of Hsp70 on SUMO modification of HIF-1α. Results The wound-healing rate of A549 and NCI-H446 cells under Hsp70 stimulation was significantly higher than blank control group. At the same time, the number of cells passing through the membrane increased significantly. Hypodermic tumor transplantation in nude mice proved that knockout Hsp70 can inhibit proliferation and metastasis of lung cancer cells. Thermal stimulation upregulated the expression of Hsp70 and promoted SUMO modification of HIF-1α, ultimately promoting the proliferation and metastasis of lung cancer. Inhibition of Hsp70 reverses the effect of thermal stimulation on lung cancer by reducing the SUMO modification of HIF-1α. Conclusion Thermal stimulation can promote EMT in A549 and NCI-H446 cells and promote cell migration and invasion in vitro and in vivo by upregulation of Hsp70. This process is associated with the promotion of SUMO modification of HIF-1α.
Highlights
Lung cancer is a serious threat to human health, and its morbidity and mortality rank first among all kinds of malignant tumors [1]
To investigate the biological effects of Hsp70, we first measured the expression of Hsp70 in human normal lung epithelial cells BEAS-2B and lung cancer cells (NCI-H460, NCI-H292, A549, and NCI-H446). e experimental results showed that the expression level of Hsp70 was upregulated in lung cancer cell lines (Figure 1(a))
QPCR was used to detect the expression of Hsp70 in tumor tissues and adjacent tissues of patients with lung cancer. e experimental results showed that the expression level of Hsp70 was increased in lung cancer tissues (Figure 1(b))
Summary
Lung cancer is a serious threat to human health, and its morbidity and mortality rank first among all kinds of malignant tumors [1]. Despite continuous advances in surgery, chemotherapy, radiation, and biological therapy, the treatment of lung cancer, especially non-small-cell lung cancer (NSCLC), has made considerable progress [2]. How to detect lung cancer early and control its invasion and metastasis effectively becomes an urgent problem to be solved in lung cancer treatment [4, 5]. Epithelial-mesenchymal transition (EMT) has recently been confirmed to be closely related to the occurrence, invasion, and metastasis of tumors. EMT phenomenon exists in lung cancer, which is related to the invasion, metastasis, and chemotherapy resistance [6,7,8]
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