scholarly journals Bone marrow mesenchymal stem cells-derived exosomal microRNA-193a reduces cisplatin resistance of non-small cell lung cancer cells via targeting LRRC1

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Hongbo Wu ◽  
Xiaoqian Mu ◽  
Lei Liu ◽  
Huijuan Wu ◽  
Xiufeng Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Colony Formation ◽  
Small Cell ◽  
Drug Resistant ◽  
Small Cell Lung ◽  
Marrow Mesenchymal Stem Cells ◽  
Resistant Cells

Abstract Exosomes are small endogenous membrane vesicles that can mediate cell communication by transferring genetic materials. Based on that, exosomes have always been discussed as a cargo carrier for microRNA (miRNA) transportation. Accumulating data have reported the inhibitory effects of microRNA-193a (miR-193a) on non-small cell lung cancer (NSCLC) cell progression. However, the mechanisms of miR-193a delivery to cancer cells and miR-193a in exosomes have not been explored clearly in NSCLC. Given that, this work aims to decode exosomal miR-193a in cisplatin (DDP) resistance of NSCLC cells. A549 and H1299 cell lines were screened out and their parent cells and drug-resistant cells were co-cultured with human bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exo) that had been transfected with miR-193a mimic or si-LRRC1 to detect the colony formation, migration, apoptosis, invasion and proliferation of NSCLC cells. In vivo experiment was conducted to verify the in vitro results. BMSC-Exo with upregulated miR-193a and downregulated LRRC1 suppressed colony formation, invasion, proliferation and migration as well as advanced apoptosis of NSCLC parent cells and drug-resistant cells. BMSC-Exo combined with upregulated miR-193a reduced tumor volume and weight in mice with NSCLC. Functional studies report that BMSC-Exo shuffle miR-193a to suppress the colony formation, invasion, migration, and proliferation as well as advance apoptosis of NSCLC DDP-resistant cells via downregulating LRRC1.

scholarly journals Intensified Beclin-1 Mediated by Low Expression of Mir-30a-5p Promotes Chemoresistance in Human Small Cell Lung Cancer

2017 ◽  
Vol 43 (3) ◽  
pp. 1126-1139 ◽  
Author(s):  
Xiang Yang ◽  
Fan Bai ◽  
Yichen Xu ◽  
Yitian Chen ◽  
Longbang Chen
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Colony Formation ◽  
Small Cell ◽  
Beclin 1 ◽  
Drug Resistant ◽  
Small Cell Lung ◽  
Resistant Cells

Background/Aims: Although small cell lung cancer (SCLC) is sensitive to initial chemotherapy, patients experience tumor recurrence and metastasis, leading to treatment failure. Autophagy as a protective pattern for cell survival in the harsh environment plays an important role in chemoresistance. However, the role of Beclin-1, a key regulator of autophagy in the drug-resistance of SCLC cells is still poorly understood. In the current study, we focused on the effect and regulation of Beclin-1 in chemoresistance of SCLC cells. Methods: We analyzed the levels of Beclin-1 in etoposide/cisplatin (EP) -resistant and -sensitive cell lines, as well as the relationship between Beclin-1 and patients’ chemosensitivity. The function of Beclin-1 in chemoresistant SCLC cells in vitro was measured by MTT, WB, colony formation and flow cytometric analysis. Further rescue experiment was performed after co-transfected with siBeclin-1 and miR-30a mimics or inhibitor. Results: Beclin-1 was upregulated in drug-resistant cells and patients with lower sensitivity to etoposide/cisplatin therapy. Downregulated Beclin-1 attenuated drug sensitivity and colony formation ability of chemoresistant cells. Moreover, inhibition of Beclin-1 resulted in a dramatic decline of autophagy and increase of apoptosis in drug-resistant cells, accompanied by a remarkable reduction in S phase and a raise in G2/M phase of cell cycle. The transfection with miR-30a-5p mimics exhibited an opposite effect. In addition, inhibition of Beclin-1 could partly reverse the effect induced by miR-30a-5p suppression in drug-sensitive cells. Conclusion: Beclin-1 regulated by miR-30a-5p plays a notable role in the drug-resistance of SCLC. Inhibition of Beclin-1 by induction of miR-30a-5p may improve the therapeutic outcome via resensitizing the drug-resistant cells to chemotherapy in SCLC.

Bone Marrow Mesenchymal Stem Cells (BMSCs) Restrain the Malignant Behaviors of A549 Lung Cancer Cells Under Hypoxia via miR-145

2022 ◽  
Vol 12 (3) ◽  
pp. 597-601
Author(s):  
Haibin Song ◽  
Heng Zhang ◽  
Lei Li
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Invasion ◽  
A549 Cells ◽  
Hypoxia Group ◽  
Marrow Mesenchymal Stem Cells ◽  
Lung Cancer Stem Cells

Deriving from bone marrow, the bone marrow mesenchymal stem cells (BMSCs) possess multipolar chemotaxis, proliferation potential, along with the capability to differentiate into various types of cells. Moreover, the hypoxic stimulation can effectively induce BMSCs differentiation. This study intends to explore the impediment of BMSCs on malignant behaviors of lung cancer stem cells under hypoxia. A co-culture system of BMSCs with A549 cells was established and then assigned into normoxia group, hypoxia group (50, 100, and 200 nmol/L) followed by analysis of cell viability by CCK-8 assay and miR-145 expression by qRT-PCR. In addition, A549 cells were grouped into NC group, miR-145-mimics group, and miR-145-inhibitors group followed by analysis of cell invasion and levels of miR-145 and Oct4. Hypoxia group exhibited a reduced cell viability and higher miR-145 expression (146.01±21.23%) compared to normoxia group (P < 0.05). Transfection of miR-145-mimic significantly upregulated miR-145 and decreased cell invasion (7.49±1.43%) compared with miR-145-inhibitors group or NC group (P < 0.05). Meanwhile, Oct4 level in miR-145-mimics group (0.934±2.98) was significantly decreased (P < 0.05). In conclusion, under hypoxia condition, the co-culture with BMSCs can upregulated miR-145 level, effectively reduce the viability of lung cancer stem cells and restrain proliferation capability.

SRC3 expressed in bone marrow mesenchymal stem cells promotes the development of multiple myeloma

2019 ◽  
Vol 51 (12) ◽  
pp. 1258-1266 ◽  
Author(s):  
Jie Jin ◽  
Shidi Cheng ◽  
Yu Wang ◽  
Tao Wang ◽  
Dongfeng Zeng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Colony Formation ◽  
Apoptosis Pathway ◽  
Promote Cell Proliferation ◽  
Mitochondrial Apoptosis Pathway ◽  
Marrow Mesenchymal Stem Cells

Abstract SRC3 plays critical roles in various biological processes of diseases, including proliferation, apoptosis, migration, and cell cycle arrest. However, the effect of SRC3 expression in mesenchymal stem cells (MSCs) on multiple myeloma (MM) is not clear yet. In our study, MSCs (MSC-SRC3, MSC-SRC3−/−) and MM cells were co-cultured in a direct or indirect way. The proliferation of MM cells was studied by CCK-8 and colony formation assays. The apoptosis and cell cycle of MM cells were detected by flow cytometry. In addition, the expressions of proteins in MM cells were detected by western blot analysis and the secretions of cytokines were measured by ELISA. Our data showed that the expression of SRC3 in bone marrow mesenchymal stem cells (BM-MSCs) could promote cell proliferation and colony formation of MM cells through accelerating the transformation of the G1/S phase, no matter what kind of culture method was adopted. Meanwhile, SRC3 expressed in BM-MSCs could inhibit the apoptosis of MM cells through the caspase apoptosis pathway and mitochondrial apoptosis pathway. Moreover, SRC3 could enhance the adhesion ability of MM cells through up-regulating the expression of adhesion molecules including CXCL4, ICAM1, VLA4, and syndecan-1. SRC3 also played a regulatory role in the progress of MM through the NF-κB and PI-3K/Akt pathways. SRC3 expressed in MSCs was found to promote the growth and survival of MM cells, while SRC3 silencing in MSCs could inhibit the development of MM. These results would be useful for developing a more effective new strategy for MM treatment.

scholarly journals Mechanism of Xu Li’s Experiential Prescription for the Treatment of EGFR-Positive NSCLC

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bin Xu ◽  
Haitao Zhang ◽  
Yuchao Wang ◽  
Shuran Huang ◽  
Li Xu
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Small Cell ◽  
Drug Resistant ◽  
M2 Macrophages ◽  
Cellular Activity ◽  
Small Cell Lung ◽  
Associated Proteins ◽  
Egfr Tki ◽  
Resistant Cells

The non-small-cell lung cancer (NSCLC) is the most common lung cancer which seriously threatens the human health. Xu Li’s experiential prescription (XLEP) can treat the NSCLC. However, whether XLEP can regulate the autophagy in the EGFR-positive NSCLC still remains unknown. We found that the cellular activity of drug-resistant cells and sensitive cells were all decreased in the TCM group and TCM + Gef group. The expression of autophagy-associated proteins (mTOR and Beclin1-Vps34) in drug-resistant cells was decreased in the TCM group, while the expression of autophagy-associated proteins in sensitive cells was all decreased in the TCM + Gef group. The ratio of M1/M2 macrophages was increased when IL-4-induced RAW264.7 was treated with TCM. TCM treatment promoted the expression of CCL2 and CCL3 while it downregulated the CCL22 level among A549, H1975, and PC9 cells. The expression of TNF-α and IL-6 was increased, and the expression of IL-10 and TGF-β was decreased in IL-4-induced RAW264.7 cells treated with TCM. And, TCM treatment also decreased the expression of Fizz1 and TGM2. In conclusion, this study indicated that XLEP could suppress the proliferation of EGFR-TKI-resistant cancer cells and increase the ratio of M1/M2 macrophages by inhibiting autophagy to treat the drug-resistant EGFR-positive NSCLC.

scholarly journals Overexpression of Osimertinib-resistant ABCG2 in Non-small cell lung cancer cells

2021 ◽  
Author(s):  
Mei Wang ◽  
Junyao Jiang ◽  
Yuxuan Du ◽  
Shuaimei Liu ◽  
Xiaojun Ge
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
High Performance ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Drug Resistant ◽  
Small Cell Lung ◽  
Resistant Cells

Abstract Objective: Osimertinib is one of the commonly used chemotherapeutic drugs for treatment of non-small cell lung cancer (NSCLC). Nonetheless, the eventual resistance developed by cancer cells to Osimertinib has led to limitations in its application. Accordingly, there is a significant need for identifying means of reversing Osimertinib resistance.Method: The CCK-8 method was employed in detecting cell proliferation and toxicity. Western blot analysis detected protein expression, cell invasion analysis was performed using transwell assays, and the concentration of Osimertinib was determined using high performance liquid chromatography (HPLC). Result: In this study, we constructed Osimertinib-resistant cells, thus indicating the vital role of ABCG2 expression in formation of drug-resistant cells. Down-regulating ABCG2 expression in drug-resistant cells can reduce the lung cancer cells’ IC50, degree of proliferation and invasion. Combining use of ERK and PI3K inhibitors to inhibit ABCG2 expression is superior to employing a single inhibitor. Conclusion: Inhibiting the expression of ABCG2 can reverse the resistance of NSCLC cells to Osimertinib. Overexpression of ABCG2 is caused by the coactivation of the MAPK and the PI3K/AKT pathways.

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