Tumor Growth
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2022 ◽  
Vol 12 (5) ◽  
pp. 964-970
Tao Liu ◽  
Xiang Wen ◽  
Qi-Jun Zhao ◽  
Ying Bai ◽  
Qing-Gang Tian

The paclitaxel is a common-used chemotherapy drug and its combination with nano albumin reduces drug side effect. However, whether nab-paclitaxel affects drug resistance of breast cancer remains unclear. This study intends to discuss the mechanism of drug resistance induced by nab-paclitaxel. The drug resistance of MCF-7/nab-paclitaxel in MCF-7 cell and cell proliferation was detected by MTT along with analysis of ABCB1 expression, cell cycle, and apoptosis. There was stronger drug resistance of nab-paclitaxel in the MCF-7/nab-paclitaxel cell group through be adopted with different concentration of nab-paclitaxel at the 0th hour, 24th hour and 48th hour. There was remarkable abnormal expression of the ABCB1 in the MCF-7/nab-paclitaxel cell group. The si-ABCB1 could release the quantity of the MCF-7/nab-paclitaxel cell blocked at S period. And the si-ABCB1 could reduce the expression of cyclin D1 and CDK2 in the MCF-7/nab-paclitaxel cell notably. But the expression level of p21 was increased when there was high concentration of si-ABCB1. The si-ABCB1 could increase the quantity of the MCF-7/nab-paclitaxel cell at the later period of cell apoptosis notably. The rat’s tumor growth was delayed obviously at the MCF-7/nabpaclitaxel cell group treated by si-ABCB1. But the inhibiting effect of the MCF-7/nab-paclitaxel cell on tumor growth was less. There was stronger drug resistance of cell for the nano albumin combined with paclitaxel. The function of cell proliferation in breast cancer was restrained by the nano albumin combined with paclitaxel mainly through inducing the expression of ABCB1, adjusting the growth of cell cycle and the expression of P21/BCL-2 protein.

2022 ◽  
Vol 12 (5) ◽  
pp. 920-925
He Bai ◽  
Jian He

The BMSCs are one of the components of tumor micro-environment and participate in tumor evolution. Our study aimed to discuss the effect of exosome derived from BMSC on gastric cancer cells. Tumor and para-tumor tissues were isolated to measure miR-206 level by RT-PCR. Gastric cancer cell behaviors were analyzed using MTT assay and scratch test. Gastric cancer model was established and treated TIGIT inhibitor to assess its role in the tumor growth in vivo. The miR-206 in exosome from BMSCs in cancer tissue was detected. CD8 expression excreted by DC could be induced after miR-206 treatment possibly through regulating the signaling pathway of TIGIT/PVR. Inhibition of TIGIT decreased tumor growth, development and reversed tumor phenotype. In conclusion, miR-206 derived from BMSCs induces CD8 expression in gastric cancer through regulating the signaling pathway of TIGIT/PVR, indicating that it might be a novel target for the treatment of gastric cancer.

Dan Wang ◽  
Dazhi Long ◽  
Jiegang Zhou ◽  
Ziqiang Dong ◽  
Guiming Huang

Background: Dexmedetomidine has been reported to induce anti-apoptotic effects and metastatic progression in lung cancer. In the current investigation, the effect of β-Caryophyllene on dexmedetomidine induced cell proliferation and apoptosis of lung cancer cells and tumor growth in mice was studied. Methods: A549 cell line was cultured with either dexmedetomidine alone or together with β-Caryophyllene for 24 h and analysed for cell proliferation with MTT assay. ELISA based kit was used to determine apoptotic DNA fragmentation. Western blotting was used to determine expression levels of target proteins. The induction of experimental lung tumor in rat model was achieved through the injection of A549 tumor cells subcutaneously into the middle left side of the mice after anesthetization with pentobarbital (35 mg/kg) at 2.8 × 106 cells in 400 μl of PBS. Result: We found that β-Caryophyllene exerts the anti-proliferative effects on A549 cells. Furthermore, β-Caryophyllene significantly prevents apoptotic cell death and causes up-regulation of PGC-1α and TFAM compared to dexmedetomidine treated cells. We observed that β-Caryophyllene suppressed tumor development in mice significantly compared to dexmedetomidine treated group without changing body weight.

Feng Qiu ◽  
Qiuchen Liu ◽  
Yanfu Xia ◽  
Hengxi Jin ◽  
Yuxin Lin ◽  

Abstract Background Epithelial-mesenchymal transition (EMT) has been associated with the angiogenesis and oncogenic phenotypes of multiple malignant tumors including bladder cancer (BCa). Circular RNAs (circRNAs) are recognized as crucial regulators in the EMT. This study aims to illustrate the possible role of circular RNA_0000658 (circ_0000658) in BCa and the underlying molecular mechanism. Methods The expression of circ_0000658, microRNA (miR)-498, and high mobility group AT-hook 2 (HMGA2) was assessed in cancer and adjacent normal tissue collected from BCa patients and human BCa cell lines (MGH-U3, T24, 5637 and SW780). BCa cells were transduced with a series of overexpression or shRNA plasmids to clarify the function of circ_0000658 and miR-498 on the oncogenic phenotypes and EMT of BCa cells. Further, we established nude mice xenografted with BCa cells to validate the roles of circ_0000658 on tumor growth in vivo. Results Circ_0000658 was highly expressed in BCa tissue samples and cell lines, which indicated a poor prognosis of BCa patients. Circ_0000658 competitively bound to miR-498 and thus restricted miR-498 expression. Meanwhile, circ_0000658 weakened the binding of miR-498 to the target gene HMGA2 and upregulated the HMGA2 expression. Circ_0000658 elevation or miR-498 knockdown augmented oncogenic phenotypes and EMT of BCa cells, corresponding to a reduction in the expression of β-catenin and E-cadherin as well as an increase in the expression of N-cadherin, Slug, Snail, ZEB1 and Twist. Inhibition of HMGA2 reversed the effects of circ_0000658 overexpression on tumor growth in vivo. Conclusion Altogether, our study uncovered the tumor-promoting role of circ_0000658 in BCa via the miR-498/HMGA2 axis.

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 173
Jee Soo Park ◽  
Myung Eun Lee ◽  
Won Sik Jang ◽  
Jongchan Kim ◽  
Se Mi Park ◽  

Immune checkpoint inhibitors and tyrosine kinase inhibitors are the first-line treatment for metastatic renal cell carcinoma (mRCC), but their benefits are limited to specific patient subsets. Here, we aimed to evaluate the therapeutic efficacy of JX-594 (pexastimogene devacirepvec, Pexa-vec) monotherapy by systemic injection in comparison with sunitinib monotherapy in metastatic orthotopic RCC murine models. Two highly metastatic orthotopic RCC models were developed to compare the treatment efficacy in the International Metastatic RCC Database Consortium favorable-risk and intermediate- or poor-risk groups. JX-594 was systemically injected through the peritoneum, whereas sunitinib was orally administered. Post-treatment, tumor microenvironment (TME) remodeling was determined using immunofluorescence analysis. Systemic JX-594 monotherapy injection demonstrated therapeutic benefit in both early- and advanced-stage mRCC models. Sunitinib monotherapy significantly reduced the primary tumor burden and number of lung metastases in the early-stage, but not in the advanced-stage mRCC model. Systemic JX-594 delivery remodeled the primary TME and lung metastatic sites by increasing tumor-infiltrating CD4/8+ T cells and dendritic cells. Systemic JX-594 monotherapy demonstrated significantly better therapeutic outcomes compared with sunitinib monotherapy in both early- and advanced-stage mRCCs by converting cold tumors into hot tumors. Sunitinib monotherapy effectively suppressed primary tumor growth and lung metastasis in early-stage mRCC.

Minghuan Mao ◽  
Liang Yang ◽  
Jingyao Hu ◽  
Bing Liu ◽  
Xiling Zhang ◽  

AbstractThe neuronally expressed developmentally downregulated 4 (NEDD4) gene encodes a ubiquitin ligase that targets the epithelial sodium channel for degradation and has been implicated in tumor growth in various cancers. Hence, in this study, we intended to characterize the functional relevance of the NEDD4-mediated Kruppel-like factor 8/microRNA-132/nuclear factor E2-related factor 2 (KLF8/miR-132/NRF2) axis in the development of bladder cancer. NEDD4 and KLF8 were overexpressed in bladder cancer tissues and were associated with poorer patient survival rates. In bladder cancer cells, NEDD4 intensified the stability and transcriptional activity of KLF8 through ubiquitination to augment cell viability and migratory ability. Our investigations revealed that NEDD4 promotes the binding of KLF8 to the miR-132 promoter region and inhibits the expression of miR-132. KLF8 inhibited the expression of miR-132 to augment the viability and migratory ability of bladder cancer cells. Furthermore, miR-132 downregulated the expression of NRF2 to restrict the viability and migratory ability of bladder cancer cells. In addition, in vivo findings verified that NEDD4 regulates the KLF8/miR-132/NRF2 axis by accelerating tumor growth and lung metastasis. In conclusion, this study highlights NEDD4 as a potential therapeutic target against tumor recurrence and metastasis in bladder cancer.

2022 ◽  
Vol 8 (1) ◽  
pp. 8
Zhen Ye ◽  
Mai Mohamed Abdelmoaty ◽  
Stephen M. Curran ◽  
Shetty Ravi Dyavar ◽  
Devendra Kumar ◽  

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after intravenous (IV) administration. We previously found that polymer complexes (polyplexes) formed between 3′-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily IV dosing. Chol-DsiRNA polyplexes, however, maintain LUC mRNA suppression for ~48 h longer after the final dose than Chol-siRNA polyplexes, which suggests that they are the better candidate formulation. Here, we directly compared the activities of Chol-siRNA polyplexes and Chol-DsiRNA polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene that is overexpressed in many solid tumors, including breast cancer. We found that Chol-siSTAT3 polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED50 0.3 mg/kg) and kinetics (over 96 h) as Chol-DsiSTAT3 polyplexes, but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated IV administration of equimolar, tumor-saturating doses every other day. Thus, both Chol-siRNA polyplexes and Chol-DsiRNA polyplexes may be suitable clinical candidates for the RNAi therapy of breast cancer and other solid tumors.

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 383
Jianlin Zhu ◽  
Lu Wang ◽  
Fan Liu ◽  
Jinghua Pan ◽  
Zhimeng Yao ◽  

Abnormal angiogenesis is one of the important hallmarks of colorectal cancer as well as other solid tumors. Optimally, anti-angiogenesis therapy could restrain malignant angiogenesis to control tumor expansion. PELP1 is as a scaffolding oncogenic protein in a variety of cancer types, but its involvement in angiogenesis is unknown. In this study, PELP1 was found to be abnormally upregulated and highly coincidental with increased MVD in CRC. Further, treatment with conditioned medium (CM) from PELP1 knockdown CRC cells remarkably arrested the function of human umbilical vein endothelial cells (HUVECs) compared to those treated with CM from wildtype cells. Mechanistically, the STAT3/VEGFA axis was found to mediate PELP1-induced angiogenetic phenotypes of HUVECs. Moreover, suppression of PELP1 reduced tumor growth and angiogenesis in vivo accompanied by inactivation of STAT3/VEGFA pathway. Notably, in vivo, PELP1 suppression could enhance the efficacy of chemotherapy, which is caused by the normalization of vessels. Collectively, our findings provide a preclinical proof of concept that targeting PELP1 to decrease STAT3/VEGFA-mediated angiogenesis and improve responses to chemotherapy due to normalization of vessels. Given the newly defined contribution to angiogenesis of PELP1, targeting PELP1 may be a potentially ideal therapeutic strategy for CRC as well as other solid tumors.

2022 ◽  
Vol 11 (2) ◽  
pp. 398
Vikash Kansal ◽  
Anshu Agarwal ◽  
Angela Harbour ◽  
Humaira Farooqi ◽  
Vijay Kumar Singh ◽  

Previously, we and others have shown that the regular intake of green tea polyphenols (GTPs) reduces ultraviolet B (UVB) radiation-induced skin cancer by targeting multiple signaling pathways, including DNA damage, DNA repair, immunosuppression, and inflammation. Here, we determine the effect of GTPs on UVB-induced epigenetic changes, emphasizing DNA hypermethylation in UV-exposed skin and tumors and their association with miR-29, a key regulator of DNA methyltransferases (DNMTs). Skin cancer was induced in SKH-1 hairless mice following repeated exposures of UVB radiation (180 mJ/cm2, three times/week, 24 weeks) with or without GTPs supplementation (0.2%) in drinking water. Regular intake of GTPs inhibited tumor growth by hindering the cascade of DNA hypermethylation events. GTPs supplementation significantly blocked UVB-induced DNA hypermethylation in the skin (up to 35%; p < 0.0001) and in tumors (up to 50%; p < 0.0001). Experimental results showed that the levels of DNA hypermethylation were higher in GTPs-treated mice than in the control group. The expressions of miR-29a, miR-29b, and miR-29c were markedly decreased in UV-induced skin tumors, and GTPs administration blocked UVB-induced miR-29s depletion. Furthermore, these observations were verified using the in vitro approach in human skin cancer cells (A431) followed by treatment with GTPs or mimics of miR-29c. Increased levels of miR-29 were observed in GTPs-treated A431 cells, resulting in increased TET activity and decreased DNA hypermethylation. In conclusion, UVB-mediated miR-29 depletion promotes DNA hypermethylation and leads to enhanced tumor growth by silencing tumor suppressors. Regular intake of GTPs rescued UVB-induced miR-29 depletion and prevented tumor growth by maintaining reduced DNA hypermethylation and activating tumor suppressors. Our observations suggest that miR-based strategies and regular consumption of GTPs could minimize the risk of UVB-induced skin cancers and contribute to better management of NMSCs.

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