Effect of AdipoR agonist in cholangiocarcinoma.

323 Background: Adiponectin is the key adipokine, which plays an important role in health and disease such as obesity, diabetes, and cancer. Adiponectin is reduced in different tumor types, especially in obesity-related cancer, and recent studies showed that Adiponectin had a potential anti-cancer effect. Obesity is a risk factor for various tumor diseases including cholangiocarcinoma (CC), the second most common primary hepatic cancer. The aim of this study is to investigate for the first time the anti-cancer effect of AdipoR agonist in CC cell lines and a CC engineered mouse model. Methods: Human CC cell lines (TFK-1 and SZ-1) and CC engineered mice (Alb-Cre/KRASG12D/p53L/L) were used to investigate the anti-cancer effects of an AdipoR agonist (2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide). Cell proliferation, migration, invasion, colony formation, apoptosis assay were applied to evaluate the effect of AdipoR agonist in vitro. In addition, important cancer signalling pathways and targets were analysed by Western Blot. Mice (n = 12) were treated with AdipoR or verhicle and tumor burden and survival were monitored. Results: AdipoR agonist suppressed proliferation, migration, invasion, colony formation and apoptosis in CC cells. AdipoR agonist regulated the expression of different proteins such as EMT markers, pAMPK, pSTAT3, and PARP, which have pivotal functions in cholangiocarcinogenesis. AdipoR agonist also prolonged survival time in a CC engineered mouse model. Conclusions: Our data revealed that AdipoR agonist inhibited successfully cell proliferation, migration, invasion, colony formation and apoptosis in vitro, and prolonged mice survival in vivo through regulation of crucial signaling pathways in cholangiocarcinogenesis. These results suggested that AdipoR agonist might become a new potential candidate for CC treatment in the future.

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Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model

Cancers ◽

10.3390/cancers11010049 ◽

2019 ◽

Vol 11 (1) ◽

pp. 49 ◽

Cited By ~ 29

Author(s):

Young Yun Jung ◽

Muthu K. Shanmugam ◽

Acharan S. Narula ◽

Chulwon Kim ◽

Jong Hyun Lee ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Mouse Model ◽

A549 Cells ◽

Xenograft Model ◽

Signaling Cascade ◽

Anticancer Effects ◽

Anti Cancer

Oxymatrine (OMT) is a major alkaloid found in radix Sophorae flavescentis extract and has been reported to exhibit various pharmacological activities. We elucidated the detailed molecular mechanism(s) underlying the therapeutic actions of OMT in non-small cell lung cancer (NSCLC) cells and a xenograft mouse model. Because the STAT5 signaling cascade has a significant role in regulating cell proliferation and survival in tumor cells, we hypothesized that OMT may disrupt this signaling cascade to exert its anticancer effects. We found that OMT can inhibit the constitutive activation of STAT5 by suppressing the activation of JAK1/2 and c-Src, nuclear localization, as well as STAT5 binding to DNA in A549 cells and abrogated IL-6-induced STAT5 phosphorylation in H1299 cells. We also report that a sub-optimal concentration of OMT when used in combination with a low dose of paclitaxel produced significant anti-cancer effects by inhibiting cell proliferation and causing substantial apoptosis. In a preclinical lung cancer mouse model, OMT when used in combination with paclitaxel produced a significant reduction in tumor volume. These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo.

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ICG-001, an Inhibitor of the β-Catenin and cAMP Response Element-Binding Protein Dependent Gene Transcription, Decreases Proliferation but Enhances Migration of Osteosarcoma Cells

Pharmaceuticals ◽

10.3390/ph14050421 ◽

2021 ◽

Vol 14 (5) ◽

pp. 421

Author(s):

Geoffroy Danieau ◽

Sarah Morice ◽

Sarah Renault ◽

Régis Brion ◽

Kevin Biteau ◽

...

Keyword(s):

Cell Proliferation ◽

Mouse Model ◽

Cell Lines ◽

Gene Transcription ◽

Pediatric Population ◽

Wnt Signaling Pathway ◽

Osteosarcoma Cell ◽

Metastatic Dissemination

High-grade osteosarcomas are the most frequent malignant bone tumors in the pediatric population, with 150 patients diagnosed every year in France. Osteosarcomas are associated with low survival rates for high risk patients (metastatic and relapsed diseases). Knowing that the canonical Wnt signaling pathway (Wnt/β-catenin) plays a complex but a key role in primary and metastatic development of osteosarcoma, the aim of this work was to analyze the effects of ICG-001, a CBP/β-catenin inhibitor blocking the β-catenin dependent gene transcription, in three human osteosarcoma cell lines (KHOS, MG63 and 143B). The cell proliferation and migration were first evaluated in vitro after ICG-001 treatment. Secondly, a mouse model of osteosarcoma was used to establish the in vivo biological effect of ICG-001 on osteosarcoma growth and metastatic dissemination. In vitro, ICG-001 treatment strongly inhibits osteosarcoma cell proliferation through a cell cycle blockade in the G0/G1 phase, but surprisingly, increases cell migration of the three cell lines. Moreover, ICG-001 does not modulate tumor growth in the osteosarcoma mouse model but, rather significantly increases the metastatic dissemination to lungs. Taken together, these results highlight, despite an anti-proliferative effect, a deleterious pro-migratory role of ICG-001 in osteosarcoma.

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PRMT1 Promoted HCC Growth and Metastasis In Vitro and In Vivo via Activating the STAT3 Signalling Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000490983 ◽

2018 ◽

Vol 47 (4) ◽

pp. 1643-1654 ◽

Cited By ~ 8

Author(s):

Xiu-Ping Zhang ◽

Ya-Bo Jiang ◽

Cheng-Qian Zhong ◽

Ning Ma ◽

Er-Bin Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Colony Formation ◽

Tumour Growth ◽

Signalling Pathway ◽

Pathway Activation ◽

And Migration ◽

Stat3 Signalling

Background/Aims: Although it has been widely accepted that protein arginine methyltransferase 1 (PRMT1) is a cancer-promoting gene in various cancers, the mechanism of PRMT1 in hepatocellular carcinoma (HCC) requires more exploration. This study aimed to investigate the role of PRMT1 in HCC growth and metastasis. Methods: We compared PRMT1 expression and clinicopathological characteristics using paired HCC and adjacent noncancerous liver tissues from 210 patients and immunohistochemistry analyses. Cell proliferation, colony formation and migration were determined in HCC cell lines with PRMT1 overexpression or downregulation through MTT, crystal violet and Boyden chamber assays. Tumour growth was monitored in a xenograft model, and intrahepatic metastasis models were established. Results: PRMT1 expression was greatly increased in clinical HCC samples and strongly associated with poor prognosis and recurrence; PRMT1 expression was also positively correlated with microvascular invasion (P = 0.024), tumour differentiation (P = 0.014), tumour size (P = 0.002), and portal vein tumour thrombus (PVTT) (P = 0.028). Cell proliferation, colony formation and migration in vitro were enhanced by PRMT1 upregulation and decreased by PRMT1 downregulation in HCC cell lines. Moreover, low PRMT1 expression resulted in slow tumour growth and decreased tumour weight in vivo, as well as tumour metastasis. These phenotypes were associated with STAT3 signalling pathway activation. Cryptotanshinone, a STAT3 inhibitor, inhibited STAT3 phosphorylation and reversed the HCC phenotype of PRMT1 expression. Conclusions: We revealed a significant role for PRMT1 in HCC progression and metastasis in vitro and in vivo via STAT3 signalling pathway activation. PRMT1 may be a potential novel prognostic biomarker and new therapeutic target for HCC.

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Estrogen Receptor 1 Inhibition of Wnt/β-Catenin Signaling Contributes to Sex Differences in Hepatocarcinogenesis

Frontiers in Oncology ◽

10.3389/fonc.2021.777834 ◽

2021 ◽

Vol 11 ◽

Author(s):

Mamatha Bhat ◽

Elisa Pasini ◽

Chiara Pastrello ◽

Marc Angeli ◽

Cristina Baciu ◽

...

Keyword(s):

Estrogen Receptor ◽

Sex Differences ◽

Mouse Model ◽

Cell Lines ◽

Target Genes ◽

Interaction Network ◽

Protein Product ◽

Tumor Burden

BackgroundHepatocellular Carcinoma (HCC) is a sexually dimorphic cancer, with female sex being independently protective against HCC incidence and progression. The aim of our study was to understand the mechanism of estrogen receptor signaling in driving sex differences in hepatocarcinogenesis.MethodsWe integrated 1,268 HCC patient sample profiles from publicly available gene expression data to identify the most differentially expressed genes (DEGs). We mapped DEGs into a physical protein interaction network and performed network topology analysis to identify the most important proteins. Experimental validation was performed in vitro on HCC cell lines, in and in vivo, using HCC mouse model.ResultsWe showed that the most central protein, ESR1, is HCC prognostic, as increased ESR1 expression was protective for overall survival, with HR=0.45 (95%CI 0.32-0.64, p=4.4E-06), and was more pronounced in women. Transfection of HCC cell lines with ESR1 and exposure to estradiol affected expression of genes involved in the Wnt/β-catenin signaling pathway. ER-α (protein product of ESR1) agonist treatment in a mouse model of HCC resulted in significantly longer survival and decreased tumor burden (p<0.0001), with inhibition of Wnt/β-Catenin signaling. In vitro experiments confirmed colocalization of β-catenin with ER-α, leading to inhibition of β-catenin-mediated transcription of target genes c-Myc and Cyclin D1.ConclusionCombined, the centrality of ESR1 and its inhibition of the Wnt/β-catenin signaling axis provide a biological rationale for protection against HCC incidence and progression in women.

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Preclinical Activity of LBH589 Alone or in Combination with Chemotherapy in a Xenogeneic Mouse Model of Human Acute Lymphoblastic Leukemia

Blood ◽

10.1182/blood.v118.21.1520.1520 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1520-1520

Author(s):

Xabier Agirre ◽

Amaia Vilas-Zornoza ◽

Gloria Abizanda ◽

Cristina Moreno ◽

Victor Segura ◽

...

Keyword(s):

Cell Proliferation ◽

Acute Lymphoblastic Leukemia ◽

Mouse Model ◽

Cell Lines ◽

Lymphoblastic Leukemia ◽

Leukemic Cells ◽

Regulatory Function ◽

Human Leukemia

Abstract Abstract 1520 Histone deacetylases (HDACs) have been identified as therapeutic targets due to their regulatory function in chromatin structure and organization. Here we analyzed the therapeutic effect of LBH589 or panobinostat, a class I-II HDAC inhibitor, in acute lymphoblastic leukemia (ALL). In vitro, LBH589 induced a significant dose-dependent increase in cell apoptosis and a markedly inhibition of cell proliferation, which were associated with increased H3 and H4 histone acetylation. While apoptosis of ALL cells was detected between 12 and 24 hours after treatment with LBH589, changes in acetylated H3 and H4 were detected as early as 2 hours. Phosphorylation of H2AX, as an early marker of DNA damaged, was detected 12 to 24 hours after in vitro treatment with LBH589. These results suggest that H3 and H4 acetylation precede DNA damaged and induction of apoptosis indicating that inhibition of HDAC is likely to be responsible at least in part for LBH589 induced apoptosis and inhibition of cell proliferation. The in vivo activity of LBH589 was initially examined in a subcutaneous ALL mouse model. The ALL cell lines TOM-1 and MOLT-4 were transplanted (1×106 cell per animal) subcutaneously into the left flanks of 6-week-old female BALB/cA-Rag2−/−γc−/−. These cell lines develop into a rapidly growing tumor. Treatment with 5mg/kg of LBH589 was initiated 24 hours after injection of the leukemic cells, included 3 cycles of 5 consecutive days of LBH589 with two days rest between cycles and animals were monitored for 24 days. A significant inhibition of tumor growth was demonstrated in animals treated with LBH589 compared with control animals (P <0.01). Inhibition of leukemia cell growth was associated with an increase in the levels of acetylated H3 and H4 and an increase in phosphorylated H2AX in the leukemic cells obtained after sacrifice of mice. These results suggest that LBH589 has a powerful antileukemic effect not only in vitro but also in vivo. Using primary ALL cells, a xenograft model of human leukemia in BALB/c-RAG2−/−γc−/− mice was established, allowing continuous passages of transplanted cells to several mouse generations. A total of 10 million cells from a patient with T-ALL (ALL-T1) and a patient with B-ALL (ALL-B1) were administered intravenously into the tail vein of 6-week-old immunodeficient female BALB/cA-Rag2−/−γc−/− mice. Kinetics of engraftment of leukemic cells was monitored in PB and BM by phenotyping while organ infiltration was analyzed by immunohistochemistry. There were no significant differences in the genome, methylome or transcriptome between the original sample and the samples obtained after multiple generations on mice. To determine the efficacy of LBH589 alone or in combination with drugs currently used for treatment of ALL, BALB/cA-RAG2−/−γc−/− mice engrafted with ALL-T1 and ALL-B1 cells were treated with LBH589, Vincristine and Dexamethasone or a combination of LBH589 with Vincristine and Dexamethasone. Treatment was initiated when disease could be detected in PB by FACS (24 hours after injection of cells for ALL-T1 and between day 17 and 21 after injection for ALL-B1). LBH589 was administered i.p. on days 1–5, 8–12 and 15–19, Vincristine i.v. on days 1, 8 and 21 and Dexamethasone daily until day 21 i.p. and survival was analyzed. Treatment of mice engrafted with T or B-ALL cells with LBH589 induced an in vivo increase in the acetylation of H3 and H4, which was accompanied with prolonged survival of LBH589-treated mice in comparison with those receiving Vincristine and Dexametasone. Notably, the therapeutic efficacy of LBH589 was significantly enhanced in combination with Vincristine and Dexametasone. Our results demonstrate the therapeutic activity of LBH589 in combination with standard chemotherapy in pre-clinical models of ALL and suggest that this combination may be of clinical value in the treatment of patients with ALL. Disclosures: No relevant conflicts of interest to declare.

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Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

Cancer Nanotechnology ◽

10.1186/s12645-021-00085-9 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Farnaz Dabbagh Moghaddam ◽

Iman Akbarzadeh ◽

Ehsan Marzbankia ◽

Mahsa Farid ◽

Leila khaledi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Treatment ◽

Cell Lines ◽

Encapsulation Efficiency ◽

Inbred Mice ◽

Breast Cancer Treatment ◽

Anticancer Effect ◽

Anti Cancer

Abstract Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

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A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway

Cancer Cell International ◽

10.1186/s12935-021-01973-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xuejie Gao ◽

Bo Li ◽

Anqi Ye ◽

Houcai Wang ◽

Yongsheng Xie ◽

...

Keyword(s):

Mouse Model ◽

Tumor Burden ◽

High Rate ◽

Cell Counting ◽

Tumor Xenograft ◽

Luciferase Reporter ◽

Therapeutic Effects ◽

Xenograft Mouse Model

Abstract Background Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity. Methods We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro. Results The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed. Conclusion The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.

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Vitamin D as Radiosensitizer: A Review in Cell Line -

Journal of Pharmacy and Nutrition Sciences ◽

10.29169/1927-5951.2020.10.06.1 ◽

2020 ◽

Vol 10 (6) ◽

pp. 315-324

Author(s):

Fahmi Radityamurti ◽

Fauzan Herdian ◽

Tiara Bunga Mayang Permata ◽

Handoko Handoko ◽

Henry Kodrat ◽

...

Keyword(s):

Vitamin D ◽

Cell Differentiation ◽

Cell Line ◽

Cell Lines ◽

Anticancer Agent ◽

Medical Literature ◽

In Vitro Studies ◽

Anti Cancer

Introduction: Vitamin D has been shown to have anti-cancer properties such as antioxidants, anti-proliferative, and cell differentiation. The property of vitamin D as an anticancer agent triggers researchers to find out whether vitamin D is useful as a radiosensitizer. Multiple studies have been carried out on cell lines in various types of cancer, but the benefits of vitamin D as a radiosensitizer still controversial. This paperwork aims to investigate the utilization of Vitamin D3 (Calcitriol) as radiosensitizer in various cell line through literature review.Methods: A systematic search of available medical literature databases was performed on in-vitro studies with Vitamin D as a radiosensitizer in all types of cell lines. A total of 11 in-vitro studies were evaluated.Results: Nine studies in this review showed a significant effect of Vitamin D as a radiosensitizer agent by promoting cytotoxic autophagy, increasing apoptosis, inhibiting of cell survival and proliferation, promoting gene in ReIB inhibition, inducing senescene and necrosis. The two remaining studies showed no significant effect in the radiosensitizing mechanism of Vitamin D due to lack of evidence in-vitro settings.Conclusion: Vitamin D have anticancer property and can be used as a radiosensitizer by imploring various mechanism pathways in various cell lines. Further research especially in-vivo settings need to be evaluated.

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Sp1-Induced Upregulation of LBX2-AS1 Aggravates The Progression of Glioblastoma By Targeting The miR-491-5p/LIF Axis

10.21203/rs.3.rs-242079/v1 ◽

2021 ◽

Author(s):

Wentao Li ◽

Ismatullah Soufiany ◽

Xiao Lyu ◽

Lin Zhao ◽

Chenfei Lu ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Cancer Progression ◽

Epithelial To Mesenchymal Transition ◽

Luciferase Reporter ◽

Mesenchymal Transition ◽

Stat3 Signaling ◽

Regulatory Effects

Abstract Background: Mounting evidences have shown the importance of lncRNAs in tumorigenesis and cancer progression. LBX2-AS1 is an oncogenic lncRNA that has been found abnormally expressed in gastric cancer and lung cancer samples. Nevertheless, the biological function of LBX2-AS1 in glioblastoma (GBM) and potential molecular mechanism are largely unclear. Methods: Relative levels of LBX2-AS1 in GBM samples and cell lines were detected by qRT-PCR and FISH. In vivo and in vitro regulatory effects of LBX2-AS1 on cell proliferation, epithelial-to-mesenchymal transition (EMT) and angiogenesis in GBM were examined through xenograft models and functional experiments, respectively. The interaction between Sp1 and LBX2-AS1 was assessed by ChIP. Through bioinformatic analyses, dual-luciferase reporter assay, RIP and Western blot, the regulation of LBX2-AS1 and miR-491-5p on the target gene leukemia Inhibitory factor (LIF) was identified. Results: LBX2-AS1 was upregulated in GBM samples and cell lines, and its transcription was promoted by binding to the transcription factor Sp1. As a lncRNA mainly distributed in the cytoplasm, LBX2-AS1 upregulated LIF, and activated the LIF/STAT3 signaling by exerting the miRNA sponge effect on miR-491-5p, thus promoting cell proliferation, EMT and angiogenesis in GBM. Besides, LBX2-AS1 was unfavorable to the progression of glioma and the survival. Conclusion: Upregulated by Sp1, LBX2-AS1 promotes the progression of GBM by targeting the miR-491-5p/LIF axis. It is suggested that LBX2-AS1 may be a novel diagnostic biomarker and therapeutic target of GBM.

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Tanshinone IIA Inhibits Osteosarcoma Growth through a Src Kinase-Dependent Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/5563691 ◽

2021 ◽

Vol 2021 ◽

pp. 1-15

Author(s):

Chao Hu ◽

Xiaobin Zhu ◽

Taogen Zhang ◽

Zhouming Deng ◽

Yuanlong Xie ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Signaling Pathways ◽

Cell Lines ◽

Src Kinase ◽

Akt Signaling ◽

Cellular Level ◽

Tanshinone Iia

Introduction. Osteosarcoma is a malignant tumor associated with high mortality rates due to the toxic side effects of current therapeutic methods. Tanshinone IIA can inhibit cell proliferation and promote apoptosis in vitro, but the exact mechanism is still unknown. The aims of this study are to explore the antiosteosarcoma effect of tanshinone IIA via Src kinase and demonstrate the mechanism of this effect. Materials and Methods. Osteosarcoma MG-63 and U2-OS cell lines were stable transfections with Src-shRNA. Then, the antiosteosarcoma effect of tanshinone IIA was tested in vitro. The protein expression levels of Src, p-Src, p-ERK1/2, and p-AKt were detected by Western blot and RT-PCR. CCK-8 assay and BrdU immunofluorescence assay were used to detect cell proliferation. Transwell assay, cell scratch assay, and flow cytometry were used to detect cell invasion, migration, and cell cycle. Tumor-bearing nude mice with osteosarcoma were constructed. The effect of tanshinone IIA was detected by tumor HE staining, tumor inhibition rate, incidence of lung metastasis, and X-ray. Results. The oncogene role of Src kinase in osteosarcoma is reflected in promoting cell proliferation, invasion, and migration and in inhibiting apoptosis. However, Src has different effects on cell proliferation, apoptosis, and cell cycle regulation among cell lines. At a cellular level, the antiosteosarcoma effect of tanshinone IIA is mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. At the animal level, tanshinone IIA played a role in resisting osteosarcoma formation by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways. Conclusion. Tanshinone IIA plays an antiosteosarcoma role in vitro and in vivo and inhibits the progression of osteosarcoma mediated by Src downstream of the MAPK/ERK and PI3K/AKt signaling pathways.

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