Carcinoma Cells
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Neoplasma ◽  
2021 ◽  
Liang-Peng Dong ◽  
Ling-Yun Chen ◽  
Bin Bai ◽  
Xiao-Fen Qi ◽  
Jing-Nan Liu ◽  

2021 ◽  
Vol 11 ◽  
Junhua Li ◽  
Wei Zhou ◽  
Qiang Mao ◽  
Dandan Gao ◽  
Lin Xiong ◽  

Chemoresistance remains as a major hindrance in the treatment of hepatocellular carcinoma (HCC). High mobility group box protein 1 (HMGB1) enhances autophagic flux and protects tumor cells from apoptosis, which results in acquired drug resistance. However, the exact mechanisms underlying HMGB1-modulated autophagy in HCC chemoresistance remain to be defined. In the present study, we found that administration of doxorubicin (DOX) significantly promoted HMGB1 expression and induced HMGB1 cytoplasmic translocation in human HCC cell lines BEL7402 and SMMC7721, which enhanced autophagy that contributes to protecting HCC cells from apoptosis and increasing drug resistance. Moreover, we observed HMGB1 translocation and elevation of autophagy in DOX-resistant BEL7402 and SMMC7721 cells. Additionally, inhibition of HMGB1 and autophagy increased the sensitivities of BEL-7402 and SMMC-7721 cells to DOX and re-sensitized their DOX-resistant cells. Subsequently, we confirmed with HMGB1 regulated autophagy by activating the 5ʹ adenosine monophosphate-activated protein kinase (AMPK)/mTOR pathway. In summary, our results indicate that HMGB1 promotes acquired DOX resistance in DOX-treated BEL7402 and SMMC7721 cells by enhancing autophagy through the AMPK/mTOR signaling pathway. These findings provide the proof-of-concept that HMGB1 inhibitors might be an important targeted treatment strategy for HCC.

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Ping Zhou ◽  
Tongdao Xu ◽  
Hao Hu ◽  
Fei Hua

Background. Thyroid carcinoma (THCA) is the most frequent endocrine malignancy. Papillary thyroid carcinoma (PTC) is the major subtype of THCA, accounting for over 80% of all THCA cases. LncRNA PAX8-AS1, a tumor suppressor associated with various human cancers, has been reported to be relevant to the regulation of all sorts of cellular processes. The purpose of this study was to verify the role of PAX8-AS1 in PTC. Methods. Three human PTC cell lines (K1, TPC-1, and IHH4) and one normal human thyroid cell line, Nthy-ori3-1, were used in our study. The expression of genes was detected by qRT-PCR. The bioinformatic analysis and luciferase reporter assay were used to confirm the binding relationship of PAX8-AS1 to miR-96-5p, and the targeting relationship of miR-96-5p to PKN2 was also predicted. Cell proliferation and apoptosis capacities were assessed by MTT and flow cytometry, respectively. EdU assay was used to detect cell proliferation. Western blot assay was employed to examine protein expression. Results. The expression of PAX8-AS1 was decreased in PTC tissues and cells. PAX8-AS1 overexpression inhibited the proliferation of PTC cells and promoted cell apoptosis. In addition, PAX8-AS1 bonds with miR-96-5p, whose downregulation elevated the expression of PKN2 in PTC cells. Importantly, according to the rescue experiments, PKN2 silencing partially reversed the inhibitory effects of PAX8-AS1 expression on PTC cell proliferation and apoptosis. Conclusions. We found that the PAX8-AS1/miR-96-5p/PKN2 axis was closely related to the progression of PTC, which could be a potential target for treating PTC patients.

Jiahui Ye ◽  
Jiajun Shi ◽  
Meng Zhang ◽  
Yin Zhang ◽  
jinqiu Tao ◽  

IntroductionIn this study, titanium nanoparticles (TiNPs) were synthesized in an aqueous medium using Alhagi maurorum extract as stabilizing and reducing agents.Material and methodsUltraviolet–visible spectrophotometry (UV-Vis), fourier-transform infrared spectroscopy (FTIR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and Energy Dispersive X-ray Spectrometry (EDS) were the techniques to characterize the biosynthetic of TiNPs. According to the XRD analysis. To survey the anti-human breast cancer effects of TiNPs, MTT assay was used on the common breast cancer cell lines i.e., breast cancer (Breast adenocarcinoma (MCF7), infiltrating ductal cell carcinoma (Hs 319.T), inflammatory carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453) cell lines.Results16.08 nm was measured for TiNPs crystal size. SEM images exhibited a uniform spherical morphology in range size of 12.16 to 43.46 nm for the biosynthesized nanoparticles respectively. The cell viability of breast carcinoma cells decreased dose-dependently in the titanium nanoparticles presence. The IC50 of A. maurorum and titanium particles on MCF7 cell line were 680 and 359 µg/mL, on Hs 319.T cell line were 507 and 191 µg/mL, on UACC-732 cell line were 477 and 217 µg/mL, and on MDA-MB-453cell line were 507 and 191 µg/mL, respectively. TiNPs had high anti-breast cancer activities dose-dependently against MCF7, Hs 319.T, UACC-732, and MDA-MB-453 cell lines.ConclusionsThe best result of anti-breast cancer effects was seen in the case of the Hs 319.T cell line.

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1527
Jing-Yan Gao ◽  
Chih-Shiang Chang ◽  
Jin-Cherng Lien ◽  
Ting-Wei Chen ◽  
Jing-Lan Hu ◽  

Trytanthrin, found in Ban-Lan-Gen, is a natural product containing an indoloquinazoline moiety and has been shown to possess anti-inflammatory and anti-viral activities. Chronic inflammation and hepatitis B are known to be associated with the progression of hepatocellular carcinoma (HCC). In this study, a series of tryptanthrin derivatives were synthesized to generate potent anti-tumor agents against HCC. This effort yielded two compounds, A1 and A6, that exhibited multi-fold higher cytotoxicity in HCC cells than the parent compound. Flow cytometric analysis demonstrated that A1 and A6 caused S-phase arrest and downregulated the expression of cyclin A1, B1, CDK2, and p-CDC2. In addition to inducing caspase-dependent apoptosis, A1 and A6 exhibited similar regulation of the phosphorylation or expression of multiple signaling targets, including Akt, NF-κB, and mitogen-activated protein kinases. The anti-tumor activities of A1 and A6 were also attributable to the generation of reactive oxygen species, accompanied by an increase in p-p53 levels. Therefore, A1 and A6 have potential clinical applications since they target diverse aspects of cancer cell growth in HCC.

2021 ◽  
Vol 11 ◽  
Cyndia Charfi ◽  
Michel Demeule ◽  
Jean-Christophe Currie ◽  
Alain Larocque ◽  
Alain Zgheib ◽  

Vasculogenic mimicry (VM) is defined as the formation of microvascular channels by genetically deregulated cancer cells and is often associated with high tumor grade and cancer therapy resistance. This microcirculation system, independent of endothelial cells, provides oxygen and nutrients to tumors, and contributes also in part to metastasis. VM has been observed in ovarian cancer and in triple negative breast cancer (TNBC) and shown to correlate with decreased overall cancer patient survival. Thus, strategies designed to inhibit VM may improve cancer patient treatments. In this study, sortilin (SORT1) receptor was detected in in vitro 3D capillary-like structures formed by ES-2 ovarian cancer and MDA-MB-231 TNBC-derived cells when grown on Matrigel. SORT1 gene silencing or antibodies directed against its extracellular domain inhibited capillary-like structure formation. In vitro, VM also correlated with increased gene expression of matrix metalloproteinase-9 (MMP-9) and of the cancer stem cell marker CD133. In vivo ES-2 xenograft model showed PAS+/CD31- VM structures (staining positive for both SORT1 and CD133). TH1904, a Doxorubicin-peptide conjugate that is internalized by SORT1, significantly decreased in vitro VM at low nM concentrations. In contrast, VM was unaffected by unconjugated Doxorubicin or Doxil (liposomal Doxorubicin) up to μM concentrations. TH1902, a Docetaxel-peptide conjugate, altered even more efficiently in vitro VM at pM concentrations. Overall, current data evidence for the first time that 1) SORT1 itself exerts a crucial role in both ES-2 and MDA-MB-231 VM, and that 2) VM in these cancer cell models can be efficiently inhibited by the peptide-drug conjugates TH1902/TH1904. These new findings also indicate that both peptide-drug conjugates, in addition to their reported cytotoxicity, could possibly inhibit VM in SORT1-positive TNBC and ovarian cancer patients.

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6356
Jiafeng Wang ◽  
Jiale Wu ◽  
Yinglong Han ◽  
Jie Zhang ◽  
Yu Lin ◽  

Two new series of betulin derivatives with semicarbazone (7a–g) or thiosemicarbazone (8a–g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, 8f displayed the most potent cytotoxicity with an IC50 value of 5.86 ± 0.61 μM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound 8f could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound 8f may be used as a valuable skeleton structure for developing novel antitumor agents.

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