scholarly journals Glucocorticoid receptor over-expression promotes human small cell lung cancer apoptosis in vivo and thereby slows tumor growth

2010 ◽  
Vol 17 (1) ◽  
pp. 203-213 ◽  
Author(s):  
Paula Sommer ◽  
Rachel L Cowen ◽  
Andrew Berry ◽  
Ann Cookson ◽  
Brian A Telfer ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Glucocorticoid Receptor ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Ectopic Acth Syndrome ◽  
Small Cell Lung ◽  
Ectopic Acth

Small cell lung cancer (SCLC) is an aggressive tumor, associated with ectopic ACTH syndrome. We have shown that SCLC cells are glucocorticoid receptor (GR) deficient, and that restoration of GR expression confers glucocorticoid sensitivity and induces apoptosis in vitro. To determine the effects of GR expression in vivo, we characterized a mouse SCLC xenograft model that secretes ACTH precursor peptides, and so drives high circulating corticosterone concentrations (analogous to the ectopic ACTH syndrome). Infection of SCLC xenografts with GR-expressing adenovirus significantly slowed tumor growth compared with control virus infection. Time to fourfold initial tumor volume increased from a median of 9 days to 16 days (P=0.05; n=7 per group). Post-mortem analysis of GR-expressing tumors revealed a threefold increase in apoptotic (TUNEL positive) cells (P<0.01). Infection with the GR-expressing adenovirus caused a significant reduction in Bcl-2 and Bcl-xL transcripts. Furthermore, in both the GR-expressing adenovirus-infected cells and tumors, a significant number of uninfected cells underwent apoptosis, supporting a bystander cell killing effect. Therefore, GR expression is pro-apoptotic for human SCLCs in vivo, as well as in vitro, suggesting that loss of GR confers a survival advantage to SCLCs.

Bradykinin-related compounds as new drugs for cancer and inflammation

2002 ◽  
Vol 80 (4) ◽  
pp. 275-280 ◽  
Author(s):  
John M Stewart ◽  
Lajos Gera ◽  
Daniel C Chan ◽  
Paul A Bunn Jr. ◽  
Eunice J York ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Small Cell ◽  
Small Cell Lung ◽  
Related Compounds

Bradykinin (BK) (Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) is an important growth factor for small-cell lung cancer (SCLC) and prostate cancer (PC). These cancers have cells of neuroendocrine origin and express receptors for a variety of neuropeptides. BK receptors are expressed on almost all lung cancer cell lines and on many PC cells. Our very potent BK antagonist B9430 (D-Arg-Arg-Pro-Hyp-Gly-Igl-Ser-D-Igl-Oic-Arg) (Hyp, trans-4-hydroxy-L-proline; Igl, α-2-indanylglycine; Oic, octahydroindole-2-carboxylic acid) is a candidate anti-inflammatory drug but does not inhibit growth of SCLC or PC. When B9430 is dimerized by N-terminal cross-linking with a suberimide linker, the product B9870 is a potent growth inhibitor for SCLC both in vitro and in vivo in athymic nude mice. Daily i.p. injection at 5 mg·kg–1·day–1 beginning on day 8 after SCLC SHP-77 cell implantation gave 65% inhibition of tumor growth. B9870 stimulates apoptosis in SCLC by a novel "biased agonist" action. We have also developed new small mimetic antagonists. BKM-570 (F5C-OC2Y-Atmp) (F5C, pentafluorocinnamic acid; OC2Y, O-2,6-dichlorobenzyl tyrosine; Atmp, 4-amino-2,2,6,6-tetramethylpiperidine) is very potent for inhibition of SHP-77 growth in nude mice. When injected daily i.p. at 5 mg·kg–1, M-570 gave 90% suppression of tumor growth. M-570 is more potent than the well-known anticancer drug cisPlatin (60% inhibition) or the recently developed SU5416 (40% inhibition) in this model. M-570 also showed activity against various other cancer cell lines in vitro (SCLC, non-SCLC, lung, prostate, colon, cervix) and inhibited growth of prostate cell line PC3 in nude mice. M-570 and related compounds evidently act in vivo through pathways other than BK receptors. These compounds have clinical potential for treatment of human lung and prostate cancers.Key words: bradykinin antagonists, cancer, inflammation, prostate cancer, small cell lung cancer.

scholarly journals Downregulation of NOB1 suppresses the proliferation and tumor growth of non-small cell lung cancer in vitro and in vivo

2014 ◽  
Vol 31 (3) ◽  
pp. 1271-1276 ◽  
Author(s):  
YANG LI ◽  
CHENGYUAN MA ◽  
MING QIAN ◽  
ZHONGMEI WEN ◽  
HONGYU JING ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals PRDX2 Promotes the Proliferation and Metastasis of Non-Small Cell Lung Cancer In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yun Chen ◽  
Sifu Yang ◽  
Hongying Zhou ◽  
Dan Su
Keyword(s):  
Lung Cancer ◽  
Tumor Growth ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Small Cell ◽  
Small Cell Lung ◽  
Bronchial Epithelial ◽  
Lung Cancer Patients

Purpose. Previous studies have reported that the levels of PRDX2 were correlated with tumorigenicity, recurrence, and prognosis of patients with different cancers. We investigated the association between PRDX2 levels and the prognosis of lung cancer patients. We also measured PRDX2 expression of non-small cell lung cancer (NSCLC) cells and examined its roles in the proliferation and migration in vitro and in vivo. Methods. We used the Kaplan–Meier plotter to analyze the survival of different levels of PRDX2 in lung cancer patients. The expression of PRDX2 in normal bronchial epithelial cell line and NSCLC cell lines was measured by qRT-PCR and western blot assays. Biological functions of NSCLC cells were detected by CCK8 and Transwell assays. We constructed tumor growth model using subcutaneously injection of nude mice and metastasis model by tail vein injection in vivo. The protein levels of proliferation related markers were measured by immunohistochemistry assay. Immunofluorescence method was used to detected EMT-related proteins. Results. The high levels of PRDX2 were associated with bad prognosis in lung cancer patients, especially in patients with adenocarcinoma. The expression of PRDX2 in NSCLC cell lines was higher than normal bronchial epithelial cells. Knockdown of PRDX2 inhibited the proliferation, migration, and invasion in A549 cells, while overexpression of PRDX2 promoted the malignancy in NCI-H1299 cells in vitro. Silencing PRDX2 restrained tumor growth and repressed lung metastasis by EMT in vivo. Conclusion. Our data indicates that PRDX2 functions as a protumor regulator and is involved in tumorigenesis and tumor progression of lung cancer.

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