Inositol hexaphosphate suppresses colorectal cancer cell proliferation via the Akt/GSK-3β/β-catenin signaling cascade in a 1,2-dimethylhydrazine-induced rat model.
Colorectal cancer (CRC) is common worldwide, and most treatments for CRC have undesirable side effects. Many researchers have demonstrated that inositol hexaphosphate (IP6) has potent anticarcinogenic activity against CRC and no apparent toxicity to normal cells. However, the underlying mechanism is still unclear. In this study, we investigated the anticancer and anti-proliferative properties of IP6 in CRC and its possible mechanisms during this chemopreventive process. We examined the expression of genes related to the PI3K/Akt and Wnt pathways at the transcriptional and translational levels in a DMH-induced rat CRC model following IP6 administration. In addition, we also conducted cell proliferation analysis. The results demonstrated that IP6 could inhibit tumors, in terms of tumor incidence, number, weight and volume in DMH-induced rats. Additionally, Akt and c-Myc mRNA levels were significantly decreased. IP6 was also shown to downregulate Akt, pAkt, pGSK-3β, and c-Myc protein expression and upregulate pβ-catenin protein expression. Furthermore, tumor tissues from IP6-treated rats showed decreased proliferation. In conclusion, the anti-proliferative effect of IP6 may be related to crosstalk between the PI3K/Akt and Wnt pathways, revealing a potential mechanism of CRC inhibition by IP6 in our model.
School of Public Health, Qingdao University Medical College, Qingdao 266021, China. Electronic address: yuwenyang1989@126.com.
Wenyang
W
Yu
School of Nursing, Qingdao University Medical College, Qingdao 266021, China. Electronic address: lcping0926@126.com.
Cuiping
C
Liu
School of Basic Medicine, Qingdao University Medical College, Qingdao 266021, China. Electronic address: lixinyiyi@126.com.
Xin
X
Li
School of Nursing, Qingdao University Medical College, Qingdao 266021, China. Electronic address: yfuguo@163.com.
Fuguo
F
Yang
School of Public Health, Qingdao University Medical College, Qingdao 266021, China. Electronic address: cchenglixue@163.com.
Lixue
L
Cheng
School of Public Health, Qingdao University Medical College, Qingdao 266021, China. Electronic address: ayerliu@yeah.net.
Chang
C
Liu
School of Public Health, Qingdao University Medical College, Qingdao 266021, China. Electronic address: qdsongyang81@163.com.
Yang
Y
Song
D019813:1,2-Dimethylhydrazine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D008297:Male; D010833:Phytic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism*
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D051176:beta Catenin; D010833:Phytic Acid; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D019813:1,2-Dimethylhydrazine
Colorectal cancer; IP6; PI3K/Akt pathway; Proliferation; Wnt pathway