Shenmai injection suppresses multidrug resistance in MCF-7/ADR cells through the MAPK/NF-κB signalling pathway

Yang, Lin; Zhang, Chengda; Chen, Jiaoting; Zhang, Sheng; Pan, Guixuan; Xin, Yanfei; Lin, Lin; You, Zhang

doi:10.1080/13880209.2020.1742167

Cited by 15 publications

(7 citation statements)

References 29 publications

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“…Recently, a new study confirmed that SMI can inhibit the function and expression of P-gp through the MAPK/NF- κ B signaling pathway and enhance the sensitivity of breast cancer cells to chemotherapy [ 25 ]. Combined with our study, SMI can also reprogram glucose metabolism, inhibit cell proliferation, and promote cell apoptosis through the Akt/mTOR/c-Myc signaling pathway, enhance the sensitivity of lung cancer cells to chemotherapy drugs, and improve the mechanism of SMI sensitization towards chemotherapy drugs.…”

Section: Discussionmentioning

confidence: 99%

Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin‐Resistant A549/DDP Cells via the AKT‐mTOR‐c‐Myc Signaling Pathway

Sun

Chen

et al. 2020

BioMed Research International

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Tumor cells, especially drug-resistant cells, predominately support growth by glycolysis even under the condition of adequate oxygen, which is known as the Warburg effect. Glucose metabolism reprogramming is one of the main factors causing tumor resistance. Previous studies on Shenmai injection (SMI), a Chinese herbal medicine, have shown enhanced efficacy in the treatment of tumors in combination with chemotherapy drugs, but the mechanism is not clear. In this study, we investigated the effect of SMI combined with cisplatin on cisplatin-resistant lung adenocarcinoma A549/DDP cells. Our results showed that cisplatin-resistant A549/DDP cells exhibited increased glucose consumption, lactate production, and expression levels of key glycolytic enzymes, including hexokinase 2 (HK2), pyruvate kinase M1/2 (PKM1/2), pyruvate kinase M2 (PKM2), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA), compared with cisplatin-sensitive A549 cells. SMI combined with cisplatin in A549/DDP cells, led to significantly lower expression levels of key glycolytic enzymes, such as HK2, PKM1/2, GLUT1, and pyruvate dehydrogenase (PDH). In addition, we found that the combination of SMI and cisplatin could inhibit cell proliferation and promote apoptosis by reducing the expression levels of p-Akt, p-mTOR, and c-Myc, and then, it reduced the glycolysis level. These results suggest that SMI enhances the antitumor effect of cisplatin via glucose metabolism reprogramming. Therefore, the combination of SMI and cisplatin may be a potential therapeutic strategy to treat cisplatin-resistant nonsmall cell lung cancer.

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Section: Discussionmentioning

confidence: 99%

Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin‐Resistant A549/DDP Cells via the AKT‐mTOR‐c‐Myc Signaling Pathway

Sun

Chen

et al. 2020

BioMed Research International

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“…The plate was shaken in the dark for 10 min, and the absorbance was measured at 490 nm by a microplate reader. The IC 50 and resistance index (RI) were calculated by SPSS normalR normalI = I C 50 normalM normalC normalF − 7 / normalT normalA normalM I C 50 normalM normalC normalF − 7 where IC 50MCF‑7/TAM is the cell median inhibition rate of MCF-7/TAM cells, IC 50MCF‑7 is the cell median inhibition rate of MCF-7 cells.…”

Section: Methodsmentioning

confidence: 99%

“…600 μL of culture medium containing 20% FBS was added to the lower chamber, incubated for 24 h, and then the supernatant was removed from the upper chamber. The drug-containing culture medium was added and incubated for 24 h. The cells were washed twice with PBS, fixed with 4% paraformaldehyde for 20 crystal violet for 15 min, and the matrix gel was removed with a cotton swab. The cells were counted under a microscope.…”

Section: Pharmacokinetic Studymentioning

confidence: 99%

Imperatorin-Loaded RH60/mPEG–PLLA Micelles for Reversing Tamoxifen Resistance in Breast Cancer

Li,

Zhao,

et al. 2024

ACS Appl. Nano Mater.

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Imperatorin (IMP) has demonstrated potential in reversing drug resistance in various tumor cells; however, its limited clinical application and development are attributed to its poor water solubility and low bioavailability. The current work is intended to enhance the oral bioavailability of IMP and its efficacy in overcoming tamoxifen (TAM) resistance in breast cancer cells. We employed mPEG−PLLA and Cremophor RH60 (RH60) to prepare imperatorin nanomicelles (IMP-RH60/mPEG−PLLA). The freeze-dried powder of IMP-RH60/mPEG−PLLA demonstrated a porous structure, and upon reconstitution, the resulting solution exhibited clarity and transparency. The particle size was measured to be 25.48 ± 0.92 nm, with a zeta potential of −5.50 ± 1.06 mV. The encapsulation efficiency was determined to be 85.78 ± 0.84%, while the drug loading was found to be 2.66 ± 0.03%. In comparison to the active pharmaceutical ingredients (APIs) of IMP, IMP-RH60/mPEG−PLLA exhibited a significant increase in in vitro release, improved bioavailability in rats, and enhanced uptake by MCF-7/TAM cells. The coadministration of IMP-RH60/mPEG−PLLA and TAM effectively inhibited the proliferation, colony formation, migration, and invasion of MCF-7/TAM cells. This outcome could potentially be attributed to the downregulation of GST-π and MDR1 drug resistance genes, consequently augmenting the susceptibility of MCF-7/TAM cells to TAM. An experimental model of BALB/c nude xenograft, consisting of human breast cancer cells resistant to tamoxifen (TAM), was established in order to assess the potential in vivo reversal of TAM resistance through the use of IMP-RH60/mPEG−PLLA. The growth of xenografts was inhibited by IMP-RH60/mPEG−PLLA, and it induced apoptosis in tumor tissues through the downregulation of K i -67, GST-π, and MDR1 gene expression. The findings indicated that the utilization of IMP-RH60/mPEG− PLLA micelles resulted in an enhancement of IMP's bioavailability and its efficacy in overcoming TAM resistance.

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“…To verify the RNA sequencing results, the mRNA levels of GADD45A and HSPB1 (HSP27) which are components of the MAPK signaling pathway (30) were assessed by RT-qPCR in Jurkat cells. Consistent with the sequencing results, GADD45A mRNA levels (1.02±0.02; 1.56±0.28; 2.63±0.41 and 4.87±0.70) and HSP27 mRNA levels (1.00±0.01, 2.04±0.51, 3.65±0.74, and 4.48±0.82) were significantly upregulated in a time-dependent manner (0, 6, 12 or 24 h) following treatment with 30 µM linalool (P<0.05; Fig.…”

Section: Linalool Inhibits T-all Cell Survival With Involvement Of Thmentioning

confidence: 99%

Linalool inhibits the growth of human T cell acute lymphoblastic leukemia cells with involvement of the MAPK signaling pathway

et al. 2020

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Linalool can inhibit the malignant proliferation of numerous human malignant solid tumors, including hepatocellular carcinoma, breast cancer, small cell carcinoma and malignant melanoma. However, the role of linalool in T cell acute lymphoblastic leukaemia (T-ALL) remains unclear. In the present study, human TALL cell lines (Jurkat, H9, Molt-4 and Raji cells) and peripheral blood mononuclear cells (PBMCs) from healthy donors were treated with various concentrations of linalool (3.75, 7.50, 15.00, 30.00, 60.00 and 120.00 µM, respectively). A CCK-8 assay was used to analyse cell viability and it demonstrated that linalool inhib ited the growth of TALL cells in a dose-dependent manner, but did not significantly affect normal PBMCs. Flow cytometry was used to detect the cell cycle and apoptosis and demonstrated that linalool reduced the percentage of TALL cells at the G 0 /G 1 phase, and induced the apoptosis of TALL cells. RNA sequencing was conducted on an Illumina HiSeq X Series 2500 before and after treatment with linalool followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. It was demonstrated that the mitogen-activated protein kinase (MAPK) pathway was involved in the effect of linalool on TALL cells. Real-time quantitative PCR and western blotting were performed to verify the mRNA and protein levels, respectively of the genes in the signaling pathway identified. In addition, it was found that linalool significantly inhibited phosphorylated (p)-ERK1/2 protein expression and enhanced p-JNK protein expression of TALL cells. In conclusion, the present study revealed that linalool inhibits TALL cell survival with involvement of the MAPK signaling pathway. JNK activation and ERK inhibition may play a functional role in apoptosis induction of TALL cells. Linalool may be developed as a novel anti TALL agent.

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Shenmai injection suppresses multidrug resistance in MCF-7/ADR cells through the MAPK/NF-κB signalling pathway

Cited by 15 publications

References 29 publications

Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin‐Resistant A549/DDP Cells via the AKT‐mTOR‐c‐Myc Signaling Pathway

Shenmai Injection Supresses Glycolysis and Enhances Cisplatin Cytotoxicity in Cisplatin‐Resistant A549/DDP Cells via the AKT‐mTOR‐c‐Myc Signaling Pathway

Imperatorin-Loaded RH60/mPEG–PLLA Micelles for Reversing Tamoxifen Resistance in Breast Cancer

Linalool inhibits the growth of human T cell acute lymphoblastic leukemia cells with involvement of the MAPK signaling pathway

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