scholarly journals Cephalosporin Antibiotics Specifically Enhance Conventional Chemotherapy in Nasopharyngeal Cancer

2020 ◽  
Author(s):  
Xiao-Qiong He ◽  
Qian Yao ◽  
Zhong Yu Song ◽  
Dan Fan ◽  
Yu Tong You ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Cancer Cells ◽  
Nasopharyngeal Cancer ◽  
Combination Group ◽  
Conventional Chemotherapy ◽  
Microarray Gene Expression ◽  
Anticancer Efficacy ◽  
Cephalosporin Antibiotics

Abstract Background: Cephalosporin antibiotics can drastically upregulate the expression of HMOX1 in nasopharyngeal carcinoma cells. HMOX1 has dual role in cancer cells, and is involved in chemoresistance. Cephalosporin antibiotics are widely used in the treatment of bacteria infectious diseases in cancer patients. Whether they affect the efficacy of chemotherapy is unknown. Methods: Comparisons between cefotaxime and the combination of cefotaxime and cisplatin were carried out throughout the study. Cell viability was detected by MTT method. Influence on clone formation of cancer cells was investigated by plate clone formation assay. The in vivo anticancer effect was determined via cancer xenograft in mice. Flow cytometry analysis was used to detect the apoptosis. Microarray gene expression profiling was analyzed using Gene Ontology analysis, and the differential genes were validated by RT-qPCR. Results: Cefotaxime specifically, selectively and synergistically enhanced the anticancer efficacy of cisplatin in nasopharyngeal carcinoma both in vitro and in vivo without increasing the toxicity, but it inhibited the cytotoxic effects of cisplatin in other cancers. Combination of cefotaxime and cisplatin significantly regulated 5 genes in direction favoring the enhancement of anticancer efficacy; of which, THBS1 and LAPTM5 were upregulated; PPP3CB, STAG1 and NCOA5 were downregulated jointly. HMOX1 contributes to the anticancer efficacy in combination group. Upregulated genes significantly modulated 18 apoptotic pathways, downregulated genes mainly affected assembly of genetic materials. Conclusion: Cephalosporin antibiotics are excellent and safe sensitizers of conventional chemotherapy in the treatment of nasopharyngeal carcinoma, but should be carefully used in other cancers.

scholarly journals Repurposing of Fluvastatin as an Anticancer Agent against Breast Cancer Stem Cells via Encapsulation in a Hyaluronan-Conjugated Liposome

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1133
Author(s):  
Ji Yu ◽  
Dae Shin ◽  
Jin-Seok Kim
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Body Weight Loss ◽  
Breast Cancer Stem Cells ◽  
Anticancer Efficacy

Fluvastatin (FLUVA), which is a common anti-hypercholesterolemia drug, exhibits potential anticancer activity as it suppresses the proliferation, angiogenesis, and metastasis of breast cancer cells via inhibiting 3-hydroxy-methyl glutaryl-coenzyme A (HMG-CoA) reductase. In this study, hyaluronan-conjugated FLUVA-encapsulating liposomes (HA-L-FLUVA) were evaluated for their anticancer efficacy in vitro and in vivo. The particle size, zeta potential, and encapsulation efficiency of HA-L-FLUVA were 158.36 ± 1.78 nm, −24.85 ± 6.26 mV, and 35%, respectively. Growth inhibition of breast cancer stem cells (BCSCs) by HA-L-FLUVA was more effective than that by free FLUVA. The half maximal inhibitory concentration (IC50) values of FLUVA, L-FLVUA, and HA-L-FLUVA were 0.16, 0.17, and 0.09 μM, respectively. The in vivo anticancer effect of HA-L-FLUVA in combination with doxorubicin (DOX) was more effective than that of free FLUVA, free DOX, and HA-L-FLUVA. The longest survival of mice was achieved by treatment with FLUVA (15 mg/kg) and HA-L-FLUVA (15 mg/kg) + DOX (3 mg/kg), followed by HA-L-FLUVA (15 mg/kg), Dulbecco’s phosphate buffered saline, and DOX (3 mg/kg). No more than 10% body weight loss was observed in the mice injected with FLUVA, indicating that the drug was not toxic. Taken together, these results indicate that HA-L-FLUVA could serve as an effective anticancer drug by inhibiting the growth of both breast cancer cells and cancer stem cells.

Preparation of Magnetic Drug Loaded Nanoparticles and Its Anticancer Efficacy Against Nasopharyngeal Carcinoma Cells

2021 ◽  
Vol 13 (5) ◽  
pp. 857-863
Author(s):  
Jingjing Chen ◽  
Cheng Kang
Keyword(s):  
Magnetic Nanoparticles ◽  
Nasopharyngeal Carcinoma ◽  
Therapeutic Effect ◽  
Inhibitory Effect ◽  
Antagonistic Effect ◽  
Anticancer Efficacy ◽  
Normal Tissues ◽  
Chemotherapy Agent

As an important drug for the treatment of cancer, cis-diamine dichloroplatinum (CDDP) has poor solubility and antagonistic effect when it is used as a chemotherapy agent alone, leading to the insufficient dose in actual administration. In order to solve the above problems, increase the targeting property of CDDP carrier and prolong the half-life period of CDDP’s sustained-release, it is necessary to design a magnetic nano-carrier for CDDP with magnetic targeting function to reduce the damage of CDDP to normal tissues in vivo and improve the therapeutic effect of cancer. Carboxymethyl chitosan (CMCS) is used to directly coat oleic acid (OA)-modified Fe3O4 nanoparticles (OA-Fe3O4 NPs) to create the nano-scale CMCS magnetic nanoparticles (CMCS/OA-Fe2O3 NPs), and CDDP loaded magnetic nanoparticles (CMCS/OA-Fe2O3 NPs/CDDP) are prepared by the bonding interaction between carboxyl groups on the surface of CMCS and the anticancer drug CDDP. The magnetic drug loaded nanoparticles are characterized, and the results show that the magnetic nanoparticles are successfully embedded in CMCS and loaded with CDDP, with the drug load of 43.65 ± 2.37%. MTT assay, flow cytometry and invasion assay are applied to evaluate the inhibitory effect of magnetic drug loaded nanoparticles to nasopharyngeal carcinoma (NPC) cells HNE-1. The results suggest that the magnetic drug loaded nanoparticles successfully prepared have significant inhibitory effect on HNE-1 cells in vitro. Therefore, the magnetic drug loaded nanoparticles prepared have a good therapeutic effect on NPC.

Telomerase is regulated by protein kinase C-ζ in human nasopharyngeal cancer cells

2001 ◽  
Vol 355 (2) ◽  
pp. 459-464 ◽  
Author(s):  
Cheng-Chou YU ◽  
Shi-Ching LO ◽  
Tzu-Chien V. WANG
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Nasopharyngeal Cancer ◽  
Telomerase Activity ◽  
Detectable Effect ◽  
Kinase C ◽  
Pkc Ζ

Telomerase, a specialized ribonucleoprotein reverse transcriptase that directs the synthesis of telomeric DNA, is repressed in normal human somatic cells, but is activated in most cancers. Little is known concerning how telomerase activity is activated and maintained in cancer cells. We have shown previously that inhibition of protein kinase C (PKC) decreases the telomerase activity of human nasopharyngeal carcinoma (NPC) cells. Here, we provide evidence that the decrease of telomerase activity by PKC inhibition is not mediated by transcriptional down-regulation of hTERT, the catalytic protein of human telomerase. In vitro phosphorylation studies revealed that exogenous addition of PKC-α, -βI, -δ or -ζ led to restoration of telomerase activity in the crude extracts of PKC-inhibited NPC cells. However, depletion of PKC-α and -βI in vivo had no detectable effect on the telomerase activity of NPC cells. Using antisense oligonucleotides against individual PKC isotypes, we observed that telomerase activity was inhibited only by the antisense oligonucleotide against PKC-ζ but not by those against PKC-α, -βI or -δ. Taken together, these data demonstrate that PKC participates in the regulation of telomerase activity by direct or indirect phosphorylation of telomerase proteins, and that PKC-ζ is the PKC isotype that functions in vivo in the NPC cells.

Inhibition of Growth of Human Nasopharyngeal Cancer Xenografts in Scid Mice by Arsenic Trioxide

2002 ◽  
Vol 88 (6) ◽  
pp. 522-526 ◽  
Author(s):  
Derui Li ◽  
Caiwen Du ◽  
Yingchen Lin ◽  
Mingyao Wu
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Arsenic Trioxide ◽  
Severe Combined Immunodeficiency ◽  
Nasopharyngeal Cancer ◽  
Intraperitoneal Administration ◽  
Scid Mice ◽  
Inhibitory Rate

Aims and background It is known that arsenic trioxide (As2O3) can induce clinical remission in patients suffering from acute promyelocytic leukemia. It has been suggested that the agent might also be effective against other malignancies. This study was done to explore the efficacy of As2O3 in the treatment of human nasopharyngeal cancer xenografts in SCID (severe combined immunodeficiency) mice. Methods Human nasopharyngeal cancer cells from the CSNE-1 cell line were implanted subcutaneously into SCID mice to produce tumors. The tumor inhibitory rate in vivo was assessed after intraperitoneal administration of As2O3. Histopathological changes in the tumor tissues and the toxicity of As2O3 to the liver, heart and kidneys of the host mice were also investigated. Results At doses of 1 mg/kg and 5 mg/kg As2O3 induced apoptosis in nasopharyngeal carcinoma cells. At 5 mg/kg As2O3 also induced cancer cell differentiation, it reduced the PCNA expression, and inhibited tumor growth. The tumor growth inhibitory rate in this experimental group was 76.02%. No nephrotoxicity was observed histologically at these dose levels but some pathological changes in liver and cardiac tissues were found. As2O3 proved lethal to the SCID mice at a dose of 10 mg/kg. Conclusion As2O3 has an inhibitory effect on human nasopharyngeal carcinoma xenografts in SCID mice. The mechanism of antitumor activity may be due, at least in part, to the induction of apoptosis and differentiation in cancer cells.

scholarly journals Cardamonin Enhances Cisplatin Chemosensitivity of Nasopharyngeal Cancer Cells via Attenuating c-Myc-Mediated β-Catenin/ABCG2 Signaling

2020 ◽  
Author(s):  
Liang Qiao ◽  
Rongzhen Li ◽  
Yahui Wu ◽  
Yujie Wang ◽  
Bin Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nasopharyngeal Carcinoma ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Nasopharyngeal Cancer ◽  
Chemotherapeutic Drugs ◽  
Nude Mouse Model ◽  
Cycle Arrest ◽  
Apoptosis Assay

Abstract Purpose: Resistance to chemotherapeutic drugs in nasopharyngeal carcinoma(NPC) remains a major obstacle of clinical therapy. To address the issue, screening for natural low-toxicity products as chemosensitizers has become a promising strategy for cancer therapy. In this study, we investigated chemosensitizing effects of cardamonin (CM), a plant-derived chalcone, on cisplatin (DPP)-resistant NPC cells, and explored the molecular mechanism for its antitumor activity. Methods: The chemotherapeutic efficacy of cardamonin, cisplatin and their combination in cisplatin-resistant NPC cells were analyzed using MTT assay, apoptosis assay, and cell cycle analysis. Real-time PCR, western blotting, and cell transfection analysis were performed to assess the synergistic inhibitory action of cardamonin supplemented with cisplatin on Wnt/β-catenin/ABCG2 signaling. The effect of cardamonin on ABCG2 drug efflux function was analyzed by doxorubicin accumulation assay. A CNE2/DPP nude mouse model was used to determine the combinatorial effects of cardamonin on tumor growth in vivo. Results: Cardamonin increased cisplatin-induced cytotoxicity, accompanied by induction of apoptosis and cell cycle arrest in DPP-resistant NPC cells. Moreover, cardamonin could synergized with cisplatin to downregulate β-catenin, c-Myc, and ABCG2. Specifically, cardamonin inhibited Wnt/β-catenin/ABCG2 signaling through c-Myc-mediated transcription inactivation, thereby suppressing the expression of ABCG2 in cisplatin-resistant NPC cells. These findings were confirmed in vivo, wherein cardamonin treatment with cisplatin resulted in reduced tumor growth in a CNE2/DPP xenograft animal model. Conclusions: Taken together, our data firstly demonstrated that cardamonin increased chemosensitivity of nasopharyngeal cancer cells to cisplatin through inactivation of Wnt/β-catenin/ABCG2 signaling, more specifically by inhibition of β-catenin/ABCG2 signaling through c-Myc-mediated transcriptional inactivation, thereby downregulation of ABCG2 and reversal of cisplatin resistance. Thus, in addition to its chemotherapeutic potential, cardamonin may serve as a useful chemosensitizer to conventional chemotherapeutic drugs in the treatment of nasopharyngeal carcinoma.

The Antitumor Activity of Betulinic Acid-Loaded Nanoliposomes Against Colorectal Cancer In Vitro and In Vivo via Glycolytic and Glutaminolytic Pathways

2020 ◽  
Vol 16 (2) ◽  
pp. 235-251
Author(s):  
Gang Wang ◽  
Yu-Zhu Wang ◽  
Yang Yu ◽  
Pei-Hao Yin ◽  
Ke Xu
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Betulinic Acid ◽  
Anticancer Efficacy ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
Cellular Apoptosis

The purpose of this study is to develop betulinic acid loaded nanoliposomes to improve the chemotherapy effect of colorectal cancer. The cellular uptake and anti-tumor effects of betulinic acid loaded nanoliposomes in vitro were characterized and evaluated, and their effects on glycolysis, glutamine decomposition and key anti-cancer targets were analyzed. Moreover, their anticancer efficacy was assessed in vivo. Compared with free betulinic acid in vitro, the cellular uptake and anti-tumor activity of betulinic acid-loaded nanoliposomes were significantly enhanced; these nanoliposomes significantly suppressed the proliferation and glucose uptake of colorectal cancer cells. Mechanistically, the anti-colorectal cancer effect of betulinic acid-loaded nanoliposomes was confirmed by their triggering of cellular apoptosis and regulating the potential glycolytic and glutaminolytic targets and pathways. After tumor proliferation was inhibited and colorectal cancer cells apoptosis, the anticancer effect of betulinic acid loaded nanoliposomes in vivo was significantly enhanced. All in all, betulinic acid loaded nanoliposomes are expected to be an effective drug delivery system for colorectal cancer treatment.

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