Hypoxia-Inducible Factor 1 Promoter-Induced JAB1 Overexpression Enhances Chemotherapeutic Sensitivity of Lung Cancer Cell Line A549 in an Anoxic Environment

Abstract

The presence of lung cancer cells in anoxic zones is a key cause od chemotherapeutic resistance. Thus, it is necessary to enhance the sensitivity of such lung cancer cells. However, loss of efficient gene therapeutic targeting and inefficient objective gene expression in the anoxic zone in lung cancer are dilemmas. In the present study, a eukaryotic expression plasmid pUC57-HRE-JAB1 driven by a hypoxia response elements promoter was constructed and introduced into lung cancer cell line A549. The cells were then exposed to a chemotherapeutic drug cis-diamminedichloroplatinum (C-DDP). qRT-PCR and western blotting were used to determine the mRNA and protein level and flow cytometry to examine the cell cycle and apoptosis of A549 transfected pUC57-HRE-JAB1. The results showed that JAB1 gene in the A549 was overexpressed after the transfection, cell proliferation being arrested in G1 phase and the apoptosis ratio significantly increased. Importantly, introduction of pUC57-HRE-JAB1 significantly increased the chemotherapeutic sensitivity of A549 in an anoxic environment. In conclusion, JAB1 overexpression might provide a novel strategy to overcome chemotherapeutic resistance in lung cancer.

miR-21 modulates paclitaxel sensitivity and hypoxia-inducible factor-1α expression in human ovarian cancer cells

“…The overexpression of P-gp has been shown to contribute to the development of drug resistance in numerous types of cancer cell (16). In the present study, flow cytometry was used to measure the expression levels of P-gp in the A2780 and A2780/taxol cells.…”

“…A previous study demonstrated that HIF-1α is involved in the development of drug resistance in several types of cancer (16), however, its role in paclitaxel sensitivity in the A2780 cell line remains unclear. To examine the correlation between HIF-1α and paclitaxel-induced cytotoxicity, HIF-1α siRNA or a scrambled siRNA was transfected into the A2780/taxol cells, followed by treatment with various doses of paclitaxel.…”

Upregulation of Id3 inhibits cell proliferation and induces apoptosis in A549/DDP human lung cancer cells in vitro

“…Apoptosis induction is an important mechanism of action of anti-cancer agents. Numerous studies have focused on the manipulation of specific genes to enhance the sensitivity of cancer cells to drugs such as the DNA-damaging agent cisplatin (28,29). High levels of Id3 have been indicated to have a role in drug resistance and disease progression and Id3 has been implicated in apoptosis in response to cisplatin.…”

Knockdown of Med19 Suppresses Proliferation and Enhances Chemo-sensitivity to Cisplatin in Non-small Cell Lung Cancer Cells

“…It has been shown that cisplatin resistance is associated with multifactorial mechanisms, such as inactivation by glutathione, metallothionein, or other sulphur-containing molecules, increased repair of DNA damage and Autophagy, reduced apoptosis and intracellular drug accumulation by changing the profile of drug-influx or -efflux molecules (Song et al, 2012;Galluzzi et al, 2012;Zhang et al, 2013). Many studies, concerned with the specific gene manipulation, have provided a way to make cancer cells specifically more sensitive to cisplatin (Hu et al, 2012;Li et al, 2012;Yu et al, 2013). However, the role of Med19 in chemotherapeutic drug resistance has not yet been established.…”