Major signalling pathways that could play significant role in lung cancer therapy include (1) Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase) (2) Growth inhibitory pathways (p53/Rb/P14ARF, STK11) (3) Apoptotic pathways (Bcl-2/Bax/Fas/FasL).
Molecular mechanisms altered in lung cancer include induced expression of oncogenes, such as RAS, MYC, c-erbB-2, and BCL-2, and loss of tumor-suppressor genes, such as RB, p53, and p16INK4A.
Overexpression of IL-22 protected lung cancer cell lines from serum starvation-induced and chemotherapeutic drug-induced apoptosis via activation of STAT3 and its downstream antiapoptotic proteins such as Bcl-2 and Bcl-xL and inactivation of extracellular signal-regulated kinase 1/2.
Previous reports have identified both Bcl-2 and Bcl-x(L) proteins as survival factors in lung cancer cells since reductions in these proteins can induce apoptosis and sensitize lung cancer cells to apoptosis induced by chemotherapy agents.
Result from the present study demonstrated that treatment with pemetrexed suppressed lung cancer cell proliferation, inhibited mRNA and protein expression levels of anti‑apoptotic Bcl2, and increased the mRNA and the protein expression levels of pro‑apoptotic p53 and apoptosis regulator BAX.
Several randomized, controlled, Phase III trials have compared standard chemotherapy with a combination of AS Bcl-2 and standard chemotherapy for the treatment of patients with chronic lymphocytic leukemia, multiple myeloma, malignant melanoma, and nonsmall cell lung carcinoma.
The BCL2 3'UTR rs1564483A allele was associated with a decreased lung cancer risk and better survival for advanced NSCLC in male Chinese, which may offer a novel biomarker for identifying high-risk population and predicting clinical outcomes.
The biologic characteristics of the two human giant-cell lung carcinoma strains with high (strain D) and low metastatic potential (strain C) were studied, including karyotype of chromosome, intracellular free calcium ([Ca2+]i), morphologic changes of cell surface and the expression of nm23-H1, p53, ras, c-myc, c-erbB2, bcl-2 genes and PCNA.
The cRL fraction up-regulated the pro-apoptotic genes p53 and Bax and induced caspase-3 activation, and down-regulated the pro-survival gene Bcl-2 in both the lung cancer cell lines.
The most frequent point mutation (A127T) enhanced lung cancer cell growth, colony formation, focal adhesion formation, and colocalized with Bcl-2 in vitro.
The most potent compound BI79D10 binds to Bcl-XL, Bcl-2, and Mcl-1 with IC50 values of 190, 360, and 520 nmol/L, respectively, and potently inhibits cell growth in the H460 human lung cancer cell line with an EC50 value of 680 nmol/L, expressing high levels of Bcl-2.
The objective of this study is to determine whether ferulenol has an anticancer effect by regulation the Bcl2 protein expression in lung cancer induced by benzo[a]pyrene in Wistar rats.
The present study concluded that baicalein combined with cisplatin induced cytotoxicity and apoptosis of A549 cells, and such activity may be associated with the regulation of Bcl-2, Bax and caspase-3, indicating a promising alternative method for lung cancer.
These findings uncover a novel mechanism of erlotinib resistance and provide a novel approach to overcome resistance by blocking the STAT3/Bcl2/Bcl-XL survival signaling pathway in human lung cancer.
These preclinical data suggested that downregulation of Bcl-2 by RNAi in the gefitinib-resistant H1975 lung cancer cell line with T790M mutation enhanced the effects of gefitinib and may offer a novel therapeutic strategy for the treatment of NSCLC.