Yanghe Huayantang Reverses Tamoxifen Resistance in Breast Cancer Through ER/PI3K/Akt/mTOR Pathway / 中国实验方剂学杂志

Objective:To explore the possible mechanism of Yanghe Huayantang in reversing the drug resistance of breast cancer by observing the effect of Yanghe Huayantang on the transplant tumor of tamoxifen （TAM）-resistant breast cancer and its influences on the interaction pathway of estrogen receptor （ER）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR）. Method:Fifty mice were randomly divided into 5 groups： blank group， model group， Yanghe Huayantang group， everolimus group， and Yanghe Huayantang+everolimus group. The model of kidney deficiency was established by bilateral ovariectomy， and the blank group was treated with sham operation. Three days after the establishment of the model， all the five groups of mice were inoculated with breast cancer TAM drug-resistant cells （MCF-7/TAM^-） to establish breast cancer TAM -resistant transplanted tumor model. After successful modeling， Yanghe Huayantang group received intragastric administration of Yanghe Huayantang （traditional Chinese medicine preparation 20 mL·kg^-1）， everolimus group received intraperitoneal injection of everolimus （10 mg·kg^-1）. Yanghe Huayantang + everolimus group received Yanghe Huayantang by intragastric administration and everolimus by intraperitoneal injection. The blank group and model group received intragastric administration and intraperitoneal injection of phosphate buffer （PBS）. Drug administration was lasted for 28 days in all groups， once a day. After administration， the tumor tissue was separated and weighed， and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of tumor tissue. Immunofluorescence and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect the expression of PI3K， Akt， mTOR， ER protein and mRNA in tumor tissue. Result:Compared with the model group， the tumor volume and tumor weight of Yanghe Huayantang group decreased significantly on the 12th， 20th and 28th days （<italic>P</italic><0.01）， and the tumor inhibition rate increased significantly （<italic>P</italic><0.01）.Yanghe Huayantang group significantly reduced the density of tumor cells and caused tumor cell necrosis. Compared with the model group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group inhibited the expression of PI3K， Akt， mTOR protein and mRNA （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the blank group， Yanghe Huayantang group， everolimus group and Yanghe Huayantang+everolimus group all inhibited the protein and mRNA expression of ER， and mRNA expression of ER in Yanghe Huayantang+everolimus group was significantly lower than that in the model group （<italic>P</italic><0.01）. Conclusion:Yanghe Huayantang can inhibit the growth of TAM-resistant breast cancer. The mechanism may be that Yanghe Huayantang can reverse the TAM resistance of breast cancer by down-regulating the expression of key molecules of ER/PI3K/Akt/mTOR cross-signal pathway.

Farnesylation-defective Rheb Increases Axonal Length Independently of mTORC1 Activity in Embryonic Primary Neurons

Rheb (Ras homolog enriched in the brain) is a small GTPase protein that plays an important role in cell signaling for development of the neocortex through modulation of mTORC1 (mammalian-target-of-rapamycin-complex-1) activity. mTORC1 is known to control various biological processes including axonal growth in forming complexes at the lysosomal membrane compartment. As such, anchoring of Rheb on the lysosomal membrane via the farnesylation of Rheb at its cysteine residue (C180) is required for its promotion of mTOR activity. To test the significance of Rheb farnesylation, we overexpressed a farnesylation mutant form of Rheb, Rheb C180S, in primary rat hippocampal neurons and also in mouse embryonic neurons using in utero electroporation. Interestingly, we found that Rheb C180S maintained promotional effect of axonal elongation similar to the wild-type Rheb in both test systems. On the other hand, Rheb C180S failed to exhibit the multiple axon-promoting effect which is found in wild-type Rheb. The levels of phospho-4EBP1, a downstream target of mTORC1, were surprisingly increased in Rheb C180S transfected neurons, despite the levels of phosphorylated mTOR being significantly decreased compared to control vector transfectants. A specific mTORC1 inhibitor, rapamycin, also could not completely abolish axon elongation characteristics of Rheb C180S in transfected cells. Our data suggests that Rheb in a non-membrane compartment can promote the axonal elongation via phosphorylation of 4EBP1 and through an mTORC1-independent pathway.

Correlations between the p-Akt-mTOR-p70S6K pathway and clinicopathological features or chemoresistance of ovarian cancer / 中南大学学报(医学版)

Objective:To study the relationship between alpha seine/threonine-protein kinase (p-Akt)-serine/ threonine-protein kinase (mTOR)-ribosomal protein S6 kinase (p70S6K) signaling pathway and clinicopathological features or chemoresistance of ovarian cancer.Methods:We checked the p-Akt,mTOR and p70S6K protein levels in 18 tissues with chemoresistance or 25 with chemosensitivity of ovarian cancer by immunohistochemistry technique,and analyzed the relationship between those proteins and clinicopathological features or chemoresistance of ovarian cancer.Results:The levels of p-Akt protein in ovarian serous carcinoma,mucinous carcinoma and endometrioid carcinoma were 77.14%,50.00% and 66.67%,respectively,with no significant difference (P>0.05).The levels of these proteins in well-middle differentiated carcinoma and low differentiated carcinoma were 73.33% and 75.00%,respectively,with no significant difference (P>0.05).The levels of these proteins in Ⅰ-Ⅱ stage carcinoma,and Ⅲ-Ⅳ stage carcinoma were 18.18% and 93.75%,respectively,with significant difference (P0.05).The levels of this protein in well-middle differentiated carcinoma and low differentiated carcinoma were 80.00% and 78.57%,respectively,with no significant difference (P>0.05).The levels of this protein in Ⅰ-Ⅱ stage carcinoma,and Ⅲ-Ⅳ stage carcinoma were 27.27% and 96.88%,respectively,with significant difference (P0.05).The levels of this protein in well-middle differentiated carcinoma and low differentiated carcinoma were 93.33% and 78.57%,respectively,with no significant difference (P>0.05).The levels of this protein in Ⅰ-Ⅱ stage carcinoma,and Ⅲ-Ⅳ stage carcinoma were 45.45% and 96.88%,respectively,with significant difference (P<0.05).The levels of p-Akt protein in tissue of chemoresistance and chemosensitivity of ovarian cancer were 88.89% and 64.00%,respectively,with significant difference (P<0.05).The levels of mTOR protein in tissue of chemoresistance and chemosensitivity of ovarian cancer were 94.44% and 68.00%,respectively,with significant difference (P<0.05).The levels of p70S6K protein in tissue of chemoresistance and chemosensitivity of ovarian cancer were 100.00% and 72.00%,respectively,with significant difference (P<0.05).Conclusion:The p-Akt-mTOR-p70S6K signaling pathway may take part in invasion and metastasis of ovarian cancer.The up-regulation of these proteins may be associated with the chemoresistance of ovarian cancer,and these proteins may have potential to be the prognostic markers for the chemoresistance of ovarian cancer.

Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes? / 대한배뇨장애요실금학회지

Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.

Targeting the Phosphatidylinositol-3-kinase Pathway in Gastric Cancer: Can Omics Improve Outcomes? / 대한배뇨장애요실금학회지

Phosphatidylinositol-3-kinase (PI3K) pathway signaling is an established oncogenic signal transduction pathway implicated in multiple malignancies. Therapeutic targeting of PI3K pathway components has improved outcomes in chronic lymphocytic leukemia, kidney cancer, breast cancer, and neuroendocrine tumors. Gastric cancers harbor some of the highest rates of oncogenic alterations in PI3K but attempts to translate this genomic observation have met with limited clinical success and novel approaches are needed. In the following review we discuss PI3K signaling, previous preclinical and clinical investigations in gastric cancer, and discuss future strategies aimed at overcoming resistance and improving efficacy. Identification and refinement of molecular tumor subtypes, development of predictive biomarkers along, and rational drug combination strategies are key to capitalizing on the therapeutic potential of PI3K pathway directed therapies in gastric cancers.

Effects of sevoflurane postconditioning on the expressions of AKT/GSK3β/mTOR during ischemia-reper-fusion in rat hearts / 临床麻醉学杂志

Objective To investigate the role of AKT/GSK3β/mTOR signaling molecule in myocardial protection of sevoflurane postconditioning.Methods Thirty-nine male Sprague-Dawley rats,weighing 200-250 g,installed in vivo myocardial ischemia-reperfusion model by left anterior de-scending coronary occlusion for 30 min.Rat hearts were randomly divided into 3 groups (n = 13 ):sham control group (group Sham),purely ischemia-reperfusion group (group IR),sevoflurane post-conditioning group (group SPC).With the exception of group Sham,each group was subjected to oc-clusion for 30 min followed by 2 h reperfusion.Group SPC was subjected to sevoflurane postcondi-tioning:2.4% sevoflurane was inhaled for 1 5 min starting from the end of ischemia until 1 5 min after beginning of reperfusion,while 33% oxygen was inhaled in the other groups.At the end of 2 h reper-fusion,cardiac function was evaluated by two-dimensional echocardiography,myocardial infarction size was measured by using 1% 2,3,5-triphenyltetrazolium chloride triazole (TTC),myocardial ultra-structural alterations was detected by transmission electron microscopy (TEM),cardiomyocytes ap-optosis was examined by terminal deoxynucleotidyl nickend labeling (TUNEL),the expressions of p-AKT/t-AKT, p-GSK3β/t-GSK3β, p-mTOR/t-mTOR,Bcl-2 and Bax proteins was measured by Western blot.Results Compared with group Sham,cardiac function was deteriorated,myocardial in-farct size was increased,cardiomyocyte mitochondrial damage was increased,positive apoptotic car-diomyocyte was increased,the expression of Bcl-2 was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bax were up-regluated in group IR (P <0.05).Compared with group IR,cardiac function was improved,myocardial infarct size was de-creased,cardiomyocyte mitochondrial damage was decreased,positive apoptotic cardiomyocyte was decreased,the expression of Bax was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bcl-2 were up-regluated in group SPC (P < 0.05 ). Conclusion Sevoflurane postconditioning can mitigate ischemia-reperfusion injury to in vivo rat hearts,decreased cardiomyocyte mitochondrial damage,inhibited cardiomyocyte apoptosis,and its mechanism was related to the activation of AKT/GSK3β/mTOR signaling molecule.

Increased Phosphorylation of PI3K/Akt/mTOR in the Obstructed Kidney of Rats with Unilateral Ureteral Obstruction / 전남의대학술지

The present study aimed to investigate changes in the mammalian target of rapamycin (mTOR) signaling pathway in the obstructed kidney of rats with unilateral ureteral obstruction (UUO). Male Sprague-Dawley rats were unilaterally obstructed by ligation of the left proximal ureter for 7 days. Control rats were treated in the same way except that no ligature was made. The expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K), Akt, and mTOR were determined in the kidney by semiquantitative immunoblotting. The protein expression levels of transforming growth factor (TGF)-beta1, Bax, and Bcl-2 were also determined in the kidney. The phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of ureteral obstruction rats compared with the control. In the obstructed kidney, the protein expression of TGF-beta1 and Bax was also increased, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the obstructed kidney of rats with UUO.

Increased Phosphorylation of PI3K/Akt/mTOR in the Obstructed Kidney of Rats with Unilateral Ureteral Obstruction / 전남의대학술지

The present study aimed to investigate changes in the mammalian target of rapamycin (mTOR) signaling pathway in the obstructed kidney of rats with unilateral ureteral obstruction (UUO). Male Sprague-Dawley rats were unilaterally obstructed by ligation of the left proximal ureter for 7 days. Control rats were treated in the same way except that no ligature was made. The expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K), Akt, and mTOR were determined in the kidney by semiquantitative immunoblotting. The protein expression levels of transforming growth factor (TGF)-beta1, Bax, and Bcl-2 were also determined in the kidney. The phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of ureteral obstruction rats compared with the control. In the obstructed kidney, the protein expression of TGF-beta1 and Bax was also increased, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the obstructed kidney of rats with UUO.

Regulation of paclitaxel-induced programmed cell death by autophagic induction: A model for cervical cancer

OBJECTIVE: Autophagy plays a vital role in homeostasis by combining organelles and cellular proteins with lysosome under starvation conditions. In addition, autophagy provides tumor cells with a source of energy. Continued autophagy will induce cells death. Here we aim to see if autophagic induction has an effect on conventional chemotherapeutic agents. METHODS: Rapamycin, or mammalian target of rapamycin and paclitaxel, apoptosis-inducing agents were used autophagy in HeLa cervical cancer cells. RESULTS: Growth inhibition of cells was not observed after the application of 0, 10, 20 nM of paclitaxel with or without rapamycin. Using a 5 nM concentration of paclitaxel, rapamycin administration inhibited cell growth significantly compared to no treatment. This implies the synergic antitumor effect of paclitaxel and rapamycin. Paclitaxel itself did not show any autophagic effect on cells but did show cell apoptosis by flow cytometry. Light chain 3, a microtubule-associated protein, which reflect autophagy, was increased with 5 nM of paclitaxel after pretreatment with 10 nM of rapamycin. CONCLUSION: These findings suggest that the autophagic inducer, rapamycin, can potentiate autophagic cell death when added as an apoptosis-inducing chemotherapeutic agent. In conclusion, the control of autophagy may be a future target for chemotherapy.

Molecules and their functions in autophagy

Autophagy is a self-degradation system of cellular components through an autophagosomal-lysosomal pathway. Over the last 15 yr, yeast genetic screens led to the identification of a number of genes involved in the autophagic pathway. Most of these autophagy genes are present in higher eukaryotes and regulate autophagy process for cell survival and homeostasis. Significant progress has recently been made to better understand the molecular mechanisms of the autophagy machinery. Especially, autophagy process, including the regulation of autophagy induction through mTOR and the nucleation and elongation in autophagosome formation through class III phosphatidylinositol 3-kinase complex and ubiquitin-like conjugation systems, became evident. While many unanswered questions remain to be answered, here, we summarize the recent process of autophagy with emphasis on molecules and their protein complexes along with advanced molecular mechanisms that regulate the autophagy machinery.

Current Status of Targeted Therapy for Advanced Renal Cell Carcinoma

The treatment of metastatic renal cell carcinoma (mRCC) has recently evolved from being predominantly cytokine-based treatment to the use of targeted agents, which include sorafenib, sunitinib, bevacizumab (plus interferon alpha [IFN-alpha]), temsirolimus, everolimus, pazopanib, and most recently, axitinib. Improved understanding of the molecular pathways implicated in the pathogenesis of RCC has led to the development of specific targeted therapies for treating the disease. In Korea, it has been 5 years since targeted therapy became available for mRCC. Thus, we now have broader and better therapeutic options at hand, leading to a significantly improved prognosis for patients with mRCC. However, the treatment of mRCC remains a challenge and a major health problem. Many questions remain on the efficacy of combination treatments and on the best methods for achieving complete remission. Additional studies are needed to optimize the use of these agents by identifying those patients who would most benefit and by elucidating the best means of delivering these agents, either in combination or as sequential single agents. Furthermore, numerous ongoing research activities aim at improving the benefits of the new compounds in the metastatic situation or their application in the early phase of the disease. This review introduces what is currently known regarding the fundamental biology that underlies clear cell RCC, summarizes the clinical evidence supporting the benefits of targeted agents in mRCC treatment, discusses survival endpoints used in pivotal clinical trials, and outlines future research directions.

Role of the mTOR Pathway in the Progression and Recurrence of Bladder Cancer: An Immunohistochemical Tissue Microarray Study

PURPOSE: Numerous trials have been conducted to develop new treatment regimens for superficial and invasive bladder cancer, because there is an urgent need to identify novel agents to prevent the recurrence and progression of these cancers. We evaluated the prognostic and biological significance of mTOR pathway-related markers in patients with bladder cancer who had undergone transurethral resection of their bladder tumors and radical cystectomy. MATERIALS AND METHODS: We retrieved 208 bladder cancer specimens collected from patients between 1989 and 2007 and constructed a tissue microarray comprising 208 tumor samples and 25 benign urothelium samples. Immunohistochemical staining was performed for mTOR, phosphorylated (phos) S6, and phos4E-BP1. The pattern, percentage, and intensity of staining for all three markers were evaluated. RESULTS: The median age at diagnosis of the patient cohort was 67 years (range: 29-87 years), and the median follow-up was 72 months (range: 1-257 months). The expression of phos4E-BP1 was higher in the bladder cancer cohort than in the benign cohort, whereas phosS6 expression was lower in the bladder cancer cohort than in the benign cohort. The expression of phosS6 was significantly higher in high-grade bladder cancer (p<0.01). There was a significant positive correlation between the H-scores of mTOR and phos4E-BP1 (coefficient of correlation, r=0.37, p<0.01) as well as between the H-scores of mTOR and phosS6 (r=0.17, p<0.05). In the multivariate analysis, strong phosS6 expression predicted shorter progression (p<0.01; hazard ratio [HR], 2.516) and disease-specific survival (p<0.01; HR, 2.396) but not overall survival (p=0.112), whereas strong phos4E-BP1 expression was a predictor of disease-specific survival (p<0.05; HR, 2.105). Moreover, strong phosS6 expression predicted shorter recurrence-free (p<0.05) and progression-free (p<0.05) survival in the superficial bladder cancer cohort. CONCLUSIONS: Our results demonstrate that mTOR pathway activation, as assessed by phos4E-BP1 phosphorylation, is related to bladder cancer tumorigenesis and that S6 protein phosphorylation is associated with a high level of disease recurrence and progression and poor cancer-specific survival.

mTOR signaling pathway and digestive system cancers / 国际肿瘤学杂志

Deregulated mTOR signaling pathway is associated closely with variety of human cancers. Preclinical and clinical studies of both classical and newly developed mTOR inhibitors in digestive system cancers show that these drugs not only have anti-tumor properties, but also can enhance tumor cells sensitivity to standard chemotherapy agents.

IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation

The scaffold protein IQGAP1 shows elevated levels in several cancer types, but its expression in hepatocellular carcinoma is unknown. We found that 58% of human hepatocellular carcinoma tissue samples had increased IQGAP1 expression compared to adjacent normal tissue. Overexpressing IQGAP1 raised the in vivo tumorigenicity of hepatocellular carcinoma cells, and forced overexpression of IQGAP1 in vitro stimulated cell proliferation. Cell growth was reduced by knockdown or mutation of IQGAP1, or by treatment of cells with a phosphotidylinositol 3-kinase inhibitor. To determine the mechanism by which IQGAP1 overexpression affected hepatocellular carcinoma cells, we confirmed its interaction in these cells with mammalian target of rapamycin (mTOR), a serine/threonine kinase that integrates signals about nutrient and energy status with downstream effectors that influence cell division. In addition, we discovered a new interaction involving IQGAP1, mTOR and Akt, which is a downstream target of mTOR. Akt phosphorylation on Ser-473, which is catalyzed by mTOR and required for Akt activation, increased with increasing amounts of IQGAP1, and decreased with IQGAP1 mutation. We hypothesize that IQGAP1 is a scaffold that facilitates mTOR and Akt interaction.

Phosphorylated Akt and Phosphorylated mTOR Expression in Breast Invasive Carcinomas: Analysis of 530 Cases / 한국유방암학회지

PURPOSE: The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway has a central role in regulation of cell proliferation, differentiation, motility and survival. This pathway has recently generated great interest because its elements are, potentially, novel targets for the treatment of various malignancies, including breast cancer. METHODS: Using tissue microarray sections of breast carcinoma, we performed immunohistochemical studies using antibodies against the phosphorylated forms of Akt (p-Akt) and mTOR (p-mTOR) in 530 invasive breast carcinomas and 30 ductal carcinomas in situ (DCIS). We investigated possible associations between expression of these proteins and clinicopathologic characteristics and disease outcomes. RESULTS: In 530 invasive carcinomas, weak and strong expression of p-Akt was observed in 180 (34.0%) and 288 (54.3%) cases, respectively. The expression of p-Akt was associated with expression of estrogen receptors (ER) (p=0.045), progesterone receptors (PR) (p=0.003), lymph node metastasis (p<0.001) and cancer stage (p=0.027). Weak and strong expression of p-mTOR was found in 136 (25.7%) and 207 (39.1%) cases, respectively. The mTOR pathway was more frequently activated in DCIS than in invasive breast carcinoma (p=0.001). p-mTOR expression was associated with expression of ER (p=0.040), PR (p=0.009), tumor size (p<0.001), and stage (p=0.002). In a univariate analysis, strong expression of p-Akt was associated with longer disease-free survival (DFS). In a multivariate analysis, neither p-Akt nor p-mTOR was associated with DFS. CONCLUSION: The PI3K/Akt/mTOR pathway is active in DCIS as well as in invasive carcinoma of the breast. Our study also suggests that the PI3K/Akt/mTOR pathway is influenced by ER rather than erbB-2, and that this pathway may contribute more to cancer pathogenesis in ER-positive tumors.

Role of phospholipase D1 in glucose-induced insulin secretion in pancreatic beta cells

As glucose is known to induce insulin secretion in pancreatic beta cells, this study investigated the role of a phospholipase D (PLD)-related signaling pathway in insulin secretion caused by high glucose in the pancreatic beta-cell line MIN6N8. It was found that the PLD activity and PLD1 expression were both increased by high glucose (33.3 mM) treatment. The dominant negative PLD1 inhibited glucose-induced Beta2 expression, and glucose-induced insulin secretion was blocked by treatment with 1-butanol or PLD1-siRNA. These results suggest that high glucose increased insulin secretion through a PLD1-related pathway. High glucose induced the binding of Arf6 to PLD1. Pretreatment with brefeldin A (BFA), an Arf inhibitor, decreased the PLD activity as well as the insulin secretion. Furthermore, BFA blocked the glucose-induced mTOR and p70S6K activation, while mTOR inhibition with rapamycin attenuated the glucose induced Beta2 expression and insulin secretion. Thus, when taken together, PLD1 would appear to be an important regulator of glucose-induced insulin secretion through an Arf6/PLD1/mTOR/p70S6K/Beta2 pathway in MIN6N8 cells.

Aberrant expression of mammalian target of rapamycin in stage ⅢB colon cancer and its significance / 解放军医学杂志

Objective To explore the aberrant expressions of mammalian target of rapamycin (mTOR) and its activation form,pmTOR,in stage IIIB human colon cancer,and analyze the association of mTOR and pmTOR with clinicopathologic characteristics and patients' prognosis. Methods A total of 104 patients with stage IIIB (T 3-4 N1M0) colon cancer with available follow-up data were enrolled. The specimens of colon cancer and clinical data were acquired from these subjects. The expressions of mTOR and pmTOR in tumor tissues and matched normal tissues were detected with immunohistochemistry. The relationship and its significance between the expressions of mTOR and pmTOR and some clinicopathological features,such as gender,age,location of primary tumor,pathological stage and TNM stage,were analyzed. Results The mTOR and pmTOR were found to be expressed in cell membrane and cytoplasm of tumor tissues. Out of the total 104 specimens,positive rate of mTOR and pmTOR accounted for 75.9% (79/104) and 76.9% (80/104),respectively. No significant correlation was noted between the expressions of mTOR and pmTOR and the clinicopathological features by partial correlation analysis. Both univariate analysis and multivariate analysis showed that the expressions of mTOR and pmTOR threw no significant influence on the 5-year overall survival of patients. Nevertheless,subgroup analysis suggested that a high expression of pmTOR along tumor border was likely to contribute to higher risk of death in patients. Conclusion Aberrant expressions of mTOR and pmTOR are noted in patients with locally advanced colon cancer. High expression of pmTOR along the border of tumor tissue may suggest the possibility of invasion and metastasis.