Targeted Delivery of Chemotherapeutic Agents for Osteosarcoma Treatment

Xie, Dizhi; Wang, Zhuqian; Li, Jie; Guo, Dean; Lu, Aiping; Liang, Chao

doi:10.3389/fonc.2022.843345

Cited by 11 publications

(14 citation statements)

References 123 publications

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“…The five-year survival rate of osteosarcoma patients with lung metastases was only 19% [3][4][5][6]. Although the diagnosis and treatment of osteosarcoma has made progress compared to the past few decades [7][8][9][10][11][12][13][14], the prognosis for patients with metastatic or recurrent cancer is still poor [15]. So, it is pivotal to study the mechanism underlying the progression of osteosarcoma and develop novel therapy targets of osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway

Cui

Dong

2022

Aging

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Researchers have reported that zinc finger CCHC domain containing 12 gene (ZCCHC12) plays a role in the progression and tumorigenesis of papillary thyroid cancer. However, the biological role of ZCCHC12 in osteosarcoma (OS) remains unknown. ZCCHC12 was highly upregulated in OS cell lines according to our present study. Also, our subsequent assays demonstrated that ZCCHC12 enhanced the proliferation, tumor growth and migration of OS cells. Moreover, the epithelial-mesenchymal transition (EMT) of OS cells was also promoted by ZCCHC12. In addition, downregulation of ZCCHC12 induced apoptosis and S-phase arrest in OS cells. Then, our study indicated that ZCCHC12 exerts its oncogenic function in OS cells by activating the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway greatly limits the oncogenic function of ZCCHC12 in OS cells. Also, overexpression of ZCCHC12 promotes tumor growth in vivo. Altogether, our study suggests ZCCHC12 promotes OS cells progression by activating the PI3K/AKT pathway. The ZCCHC12 gene may be a novel diagnostic and therapeutic target for OS.

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Section: Introductionmentioning

confidence: 99%

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway

Cui

Dong

2022

Aging

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“…Osteosarcoma (OS) is the most common primary malignant bone tumor, and represents the second leading cause of cancer-related death in children and adolescents [ 1 , 2 ]. Surgery combined with multimodal chemotherapy, comprising doxorubicin, methotrexate and cisplatin (CDDP), is the standard treatment for OS patients [ 3 , 4 ]. CDDP, an alkylating agent, functions in a cell-cycle-independent manner to cause DNA damage and cell death through alkylated DNA adducts [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Curcumol Synergizes with Cisplatin in Osteosarcoma by Inhibiting M2-like Polarization of Tumor-Associated Macrophages

et al. 2022

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Osteosarcoma is the most prevalent bone cancer, and chemotherapy is still an indispensable treatment in its clinical practice. Cisplatin (CDDP) has become the most commonly used agent for osteosarcoma, although the outcomes of CDDP chemotherapy remain unsatisfactory because of frequent resistance. Here, we report on a promising combination therapy where curcumol, a bioactive sesquiterpenoid, enhanced CDDP-induced apoptosis to eradicate osteosarcoma cells, and revealed that M2-like macrophages might be the underlying associated mechanisms. First, we observed that curcumol enhanced the CDDP-mediated inhibition of cell proliferation and augmented the apoptosis in osteosarcoma cell lines. Curcumol contributed to preventing the migration of osteosarcoma cells when combined with CDDP. Moreover, this drug combination showed more potent tumor-growth suppression in the orthotopic transplantation of osteosarcoma K7M2 WT cells. We then estimated chemotherapy-associated drug-resistant genes, including ABCB1, ABCC1 and ABCG2, and found that curcumol significantly reversed the mRNA levels of CDDP-induced ABCB1, ABCC1 and ABCG2 genes in the tumor tissue. Moreover, M2-like macrophages were enriched in osteosarcoma tissues, and were largely decreased after curcumol and CDDP treatment. Taken together, these findings suggest that curcumol inhibits the polarization of M2-like macrophages and could be a promising combination strategy to synergize with CDDP in the osteosarcoma.

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“…The conventional therapy for osteosarcoma includes surgery, neoadjuvant, radiotherapy and chemotherapy (3,4). The five-year survival rate is unsatisfactory in osteosarcoma patients because of the lack of early detection and development of metastasis as well as radio-resistance and drug resistance (5)(6)(7). Moreover, the molecular mechanisms of osteosarcoma development and progression are not fully determined.…”

Section: Introductionmentioning

confidence: 99%

LncRNA SCAMP1 disrupts the balance between miR-26a-5p and ZEB2 to promote osteosarcoma cell viability and invasion

Chen

Zhou

et al. 2022

Front. Oncol.

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Osteosarcoma often occurs in children and adolescents and affects their health. The survival rate of osteosarcoma patients is unsatisfactory due to the lack of early detection and metastasis development and drug resistance. Hence, dissection of molecular insight into osteosarcoma initiation and progression is pivotal to provide the new therapeutic strategy. In recent years, long noncoding RNAs (lncRNAs) have burst into stage in osteosarcoma development and malignant behaviors. LncRNA SCAMP1 has been discovered to play an essential role in carcinogenesis and progression. However, the mechanisms of lncRNA SCAMP1-involved tumorigenesis have not been reported in human osteosarcoma. In this study, we utilized multiple cellular biological approaches to determine the function of lncRNA SCAMP1 in osteosarcoma cells. Moreover, we performed several molecular biological approaches to define the mechanism by which lncRNA SCAMP1 regulated cell viability and invasion in osteosarcoma. We dissected that lncRNA SCAMP1 promoted progression of osteosarcoma via modulation of miR-26a-5p/ZEB2 axis. In conclusion, targeting lncRNA SCAMP1 and its downstream targets, miR-26a-5p and ZEB2, might be a useful approach for osteosarcoma therapy.

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Targeted Delivery of Chemotherapeutic Agents for Osteosarcoma Treatment

Cited by 11 publications

References 123 publications

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway

ZCCHC12 promotes the progression of osteosarcoma via PI3K/AKT pathway

Curcumol Synergizes with Cisplatin in Osteosarcoma by Inhibiting M2-like Polarization of Tumor-Associated Macrophages

LncRNA SCAMP1 disrupts the balance between miR-26a-5p and ZEB2 to promote osteosarcoma cell viability and invasion

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