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Inhibition of JAK2/STAT3 signalling induces colorectal cancer cell apoptosis via mitochondrial pathway.

Du W, Hong J, Wang YC, Zhang YJ, Wang P, Su WY, Lin YW, Lu R, Zou WP, Xiong H, Fang JY - J. Cell. Mol. Med. (2012)

Bottom Line: In addition, our results demonstrated that the translocation of cytochrome c (Cyt c), caspase activation and cleavage of poly (ADP-ribose) polymerase (PARP) were present in apoptotic CRC cells after down-regulation of JAK2/STAT3 signalling.Our findings illustrated the biological significance of JAK2/STAT3 signalling in CRC apoptosis, and provided novel evidence that inhibition of JAK2/STAT3 induced apoptosis via the mitochondrial apoptotic pathway.Therefore, JAK2/STAT3 signalling may be a potential target for therapy of CRC.

View Article: PubMed Central - PubMed

Affiliation: GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Shanghai, China.

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Suppression of established tumour growth in nude mice by AG490 and STAT3 siRNA. (A) AG490 and STAT3 siRNA suppressed SW1116 xenograft tumour growth. Tumour volume was smaller compared with the negative group after treatments. Representative photographs of a mouse in each SW1116 xenograft group are shown. The tumour volumes measurements are means ± S.D. (n = 6). (B) JAK2/STAT3 signalling and caspase cascade in SW1116 xenografts mice analysed by Western blot.
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fig06: Suppression of established tumour growth in nude mice by AG490 and STAT3 siRNA. (A) AG490 and STAT3 siRNA suppressed SW1116 xenograft tumour growth. Tumour volume was smaller compared with the negative group after treatments. Representative photographs of a mouse in each SW1116 xenograft group are shown. The tumour volumes measurements are means ± S.D. (n = 6). (B) JAK2/STAT3 signalling and caspase cascade in SW1116 xenografts mice analysed by Western blot.

Mentions: To determine whether components of JAK2/STAT3 could serve as therapeutic targets, we established a tumour model in nude mice bearing SW1116 xenografts. After treatment with different concentrations of AG490, we found that the tumour volume of the high dose group (15 mg/kg) was smaller than that of the low dose group (10 mg/kg) without obviously toxicity (P < 0.05). Moreover, transient transfection of STAT3 siRNA also led to the slower growth of SW1116 xenografts when compared with the mock or NC animal group (Fig. 6A).


Inhibition of JAK2/STAT3 signalling induces colorectal cancer cell apoptosis via mitochondrial pathway.

Du W, Hong J, Wang YC, Zhang YJ, Wang P, Su WY, Lin YW, Lu R, Zou WP, Xiong H, Fang JY - J. Cell. Mol. Med. (2012)

Suppression of established tumour growth in nude mice by AG490 and STAT3 siRNA. (A) AG490 and STAT3 siRNA suppressed SW1116 xenograft tumour growth. Tumour volume was smaller compared with the negative group after treatments. Representative photographs of a mouse in each SW1116 xenograft group are shown. The tumour volumes measurements are means ± S.D. (n = 6). (B) JAK2/STAT3 signalling and caspase cascade in SW1116 xenografts mice analysed by Western blot.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822699&req=5

fig06: Suppression of established tumour growth in nude mice by AG490 and STAT3 siRNA. (A) AG490 and STAT3 siRNA suppressed SW1116 xenograft tumour growth. Tumour volume was smaller compared with the negative group after treatments. Representative photographs of a mouse in each SW1116 xenograft group are shown. The tumour volumes measurements are means ± S.D. (n = 6). (B) JAK2/STAT3 signalling and caspase cascade in SW1116 xenografts mice analysed by Western blot.
Mentions: To determine whether components of JAK2/STAT3 could serve as therapeutic targets, we established a tumour model in nude mice bearing SW1116 xenografts. After treatment with different concentrations of AG490, we found that the tumour volume of the high dose group (15 mg/kg) was smaller than that of the low dose group (10 mg/kg) without obviously toxicity (P < 0.05). Moreover, transient transfection of STAT3 siRNA also led to the slower growth of SW1116 xenografts when compared with the mock or NC animal group (Fig. 6A).

Bottom Line: In addition, our results demonstrated that the translocation of cytochrome c (Cyt c), caspase activation and cleavage of poly (ADP-ribose) polymerase (PARP) were present in apoptotic CRC cells after down-regulation of JAK2/STAT3 signalling.Our findings illustrated the biological significance of JAK2/STAT3 signalling in CRC apoptosis, and provided novel evidence that inhibition of JAK2/STAT3 induced apoptosis via the mitochondrial apoptotic pathway.Therefore, JAK2/STAT3 signalling may be a potential target for therapy of CRC.

View Article: PubMed Central - PubMed

Affiliation: GI Division, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai Institution of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology, Shanghai, China.

Show MeSH
Related in: MedlinePlus