Expression of insulin-like growth factor-1 receptor in human colorectal cancer

Hakam, Ardeshir; Yeatman, Timothy J.; Lü, Li; Mora, Linda; Marcet, George; Nicosia, Santo V.; Karl, Richard C.; Coppola, Domenico

doi:10.1016/s0046-8177(99)90027-8

Cited by 210 publications

(161 citation statements)

References 25 publications

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“…Curcumin has also been shown to be an effective inhibitor of cell growth in prostatglandin-synthesis deficient cancer cells (HCT-15), suggesting that it may also act via prostaglandin independent pathways. 12 Our current data, for the first time, demonstrate that curcumin acts synergistically with FOLFOX in inhibiting the growth of colon cancer cells. This could be attributed to attenuation of not only EGFRs but also IGF-1R activation and their subsequent downstream signaling.…”

Section: Discussionmentioning

confidence: 50%

Curcumin enhances the effects of 5‐fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF‐1R

Patel

Sengupta

Qazi

et al. 2007

Intl Journal of Cancer

196

133

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Curcumin (diferuloylmethane), which has been shown to inhibit growth of transformed cells, has no discernible toxicity and achieves high levels in colonic mucosa. 5-fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but with limited success. The present investigation was, therefore, undertaken to examine whether curcumin in combination with conventional chemotherapeutic agent(s)/regimen will be a superior therapeutic strategy for colorectal cancer. Indeed, results of our in vitro studies demonstrated that curcumin together with FOLFOX produced a significantly greater inhibition (p < 0.01) of growth and stimulated apoptosis (p < 0.001) of colon cancer HCT-116 and HT-29 cells than that caused by curcumin, 5-FU, curcumin 1 5-FU or FOLFOX. These changes were associated with decreased expression and activation (tyrosine phosphorylation) of EGFR, HER-2, HER-3 (72-100%) and IGF-1R (67%) as well as their downstream effectors such as Akt and cycloxygenase-2 (51-97%). Furthermore, while these agents produced a 2-3-fold increase in the expression of IGF-binding protein-3 (IGFBP-3), curcumin together with FOLFOX caused a 5-fold increase in the same, when compared to controls. This in turn led to increased sequestration of IGF by IGFBP-3 rendering IGF-1 unavailable for binding to and activation of IGF-1R. We conclude that the superior effects of the combination therapy of curcumin and FOLFOX are due to attenuation of EGFRs and IGF-1R signaling pathways. We also suggest that inclusion of curcumin to the conventional chemotherapeutic agent(s)/regimen could be an effective therapeutic strategy for colorectal cancer. ' 2007 Wiley-Liss, Inc.Key words: colorectal cancer; EGFR; IGF-1R; curcumin; chemotherapy; IGFBP3There will be an estimated 148,610 new cases and 55,170 deaths due to colorectal caner (CRC) in 2006 in the USA. 1 CRC is estimated to be the second and third leading cause of cancerrelated deaths in men and women, respectively, in 2006. 1 Surgery and subsequent chemotherapy can cure over 75% colon cancer patients, but more than 30% of these patients develop new neoplastic polyps, and 10% progress to frank second malignancy. [2][3][4] The risk of second malignancy is higher for microsatellite instable tumor (MSI). 5 Metastatic colorectal cancer has poor a prognosis with 5-year survival of less than 10%. 6 As a result of great efforts are being spent on improving chemotherapeutic interventions for metastatic colon cancer, and the median survival has improved to over 20 months of this group of patients. 7 However, this comes at a cost of additional toxicities, some of which are even fatal. 7 The validation of a nontoxic agent that could improve upon the current chemotherapeutic regimen would therefore be highly desirable.Accumulating evidence suggests that the development and progression of many malignancies, including colorectal cancer, are associated with constitutive activation of multiple signaling pathways that promote proliferation, inhibit apoptosis an...

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Section: Discussionmentioning

confidence: 50%

Curcumin enhances the effects of 5‐fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF‐1R

Patel

Sengupta

Qazi

et al. 2007

Intl Journal of Cancer

196

133

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“…10 IGF-IR has been found to be overexpressed in various human cancer types including breast, prostate, lung, osteosarcoma, gastric and colon cancer. [11][12][13][14] In many tumor cells, including non small cell and small cell lung carcinomas and mesotheliomas, a high level of expression of IGF-IR and IGF-I can act in an autocrine fashion. [15][16][17][18] It has been well established that overexpression and/or constitutive activation of IGF-IR in a variety of fibroblast types lead to ligand-dependent growth in serum-free medium and to the establishment of a transformed phenotype as demonstrated by the development of tumors in nude mice.…”

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confidence: 99%

A recombinant humanized anti‐insulin‐like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti‐epidermal growth factor receptor therapy against human cancer xenografts

Goetsch

Gonzalez

Léger

et al. 2004

Intl Journal of Cancer

197

152

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“…Normal mucosa, adjacent to the carcinomas (34 cases), was negative. Strong IGF-1R positivity correlated with higher grade and higher-stage tumors (p<0.01) [10].…”

Section: Laboratory Studiesmentioning

confidence: 90%

“…In a retrospective study, the expression of IGF-1R in 12 colonic adenomas, 36 primary CRCs, and 27 corresponding metastases was investigated [10]. Moderate to strong cytoplasmic immunostaining with anti-IGF-1R rabbit polyclonal antibody was observed in 96% of carcinoma cases and 93% of metastases.…”

Section: Laboratory Studiesmentioning

confidence: 99%

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Role of insulin-like growth factor-1R system in colorectal carcinogenesis

Donovan

Kummar

2008

Critical Reviews in Oncology/Hematology

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The insulin-like growth factor (IGF) system is comprised of receptors, ligands (IGF-I and IGF-II), and a family of binding proteins (IGFBPs). It plays an important role in growth and development and in the maintenance of normal homeostasis. We present a review of the current laboratory and epidemiologic evidence that suggests an important role of the IGF system in colorectal carcinogenesis. Due to the complexity of this system, we have focused the review on the role of the IGF-1 receptor and its ligands in colorectal carcinogenesis and the strategies to block this pathway as a potential anti-cancer therapy.

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Expression of insulin-like growth factor-1 receptor in human colorectal cancer

Cited by 210 publications

References 25 publications

Curcumin enhances the effects of 5‐fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF‐1R

Curcumin enhances the effects of 5‐fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF‐1R

A recombinant humanized anti‐insulin‐like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti‐epidermal growth factor receptor therapy against human cancer xenografts

Role of insulin-like growth factor-1R system in colorectal carcinogenesis

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