Organoid model: A new hope for pancreatic cancer treatment?

Chen, Haidi; Zhuo, Qifeng; Zeng, Ye; Xu, Xiaowu; Ji, Shunrong

doi:10.1016/j.bbcan.2020.188466

Cited by 39 publications

(21 citation statements)

References 76 publications

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“…Pancreatic cancer (PC) is responsible for the fourth highest number of tumor-related deaths worldwide [ 1 ]. Although therapeutic options for patients with PC have improved, the 5-year survival rate for patients with PC is still <5% [ 2 , 3 ]. The poor prognosis for patients with PC is caused by the high proliferation and early invasion of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression

Cai

Zeng

et al. 2022

Cell Death Dis

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Dysregulation of autophagy and circular RNAs (circRNAs) are involved in the pancreatic cancer (PC) progression. However, the regulatory network between circRNAs, autophagy, and PC progression remains unknown. Herein, we demonstrated that autophagy-associated circRNA circ-autophagy related 7 (circATG7) was elevated in PC tissues compared to adjacent tissues, and in PC cells treated with EBSS and hypoxia. circATG7 expression was positively associated with tumor diameter and lymph node invasion in patients with PC. circATG7 overexpression promoted PC cell proliferation, mobility, and autophagy in vitro, while circATG7 knockdown induced the opposite effects. ATG7 inhibition attenuated the effects of circATG7 on the biological functions of PC cells. CircATG7 is located in the cell cytoplasm and nucleus. Cytoplasmic circATG7 sponged miR-766-5p and decreased its expression, and increased the expression of ATG7, a target gene of miR-766-5p. Nuclear circATG7 acted as a scaffold to increase the interaction between the human antigen R protein and ATG7 mRNA and enhanced ATG mRNA stability. Furthermore, we demonstrated that circATG7 regulates PC cell proliferation and metastasis in vivo via ATG7-dependent autophagy. In conclusion, our results demonstrated that circATG7 accelerates PC progression via miR-766-5p/ATG7 and that HUR/ATG7 depends on autophagic flux. Thus, circATG7 may be a potential therapeutic target for PC.

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Section: Introductionmentioning

confidence: 99%

Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression

Cai

Zeng

et al. 2022

Cell Death Dis

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“…For the latter, the existing methods on the construction of organoids are challenging to standardize since organic-like material needs to be cultivated in droplets of solidified substrates indispensably. The local differences in physical parameters and accessibility of growth factors result in variations in the shape, size, and distribution of organoids [ 20 ]. So, it is challenging to develop a reliable and stable system to decipher the tumor environment.…”

Section: Introductionmentioning

confidence: 99%

Honeycomb-Like Hydrogel Microspheres for 3D Bulk Construction of Tumor Models

Chen

et al. 2022

Research

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A two-dimensional (2D) cell culture-based model is widely applied to study tumorigenic mechanisms and drug screening. However, it cannot authentically simulate the three-dimensional (3D) microenvironment of solid tumors and provide reliable and predictable data in response to in vivo, thus leading to the research illusions and failure of drug screening. In this study, honeycomb-like gelatin methacryloyl (GelMA) hydrogel microspheres are developed by synchronous photocrosslinking microfluidic technique to construct a 3D model of osteosarcoma. The in vitro study shows that osteosarcoma cells (K7M2) cultured in 3D GelMA microspheres have stronger tumorous stemness, proliferation and migration abilities, more osteoclastogenetic ability, and resistance to chemotherapeutic drugs (DOX) than that of cells in 2D cultures. More importantly, the 3D-cultured K7M2 cells show more tumorigenicity in immunologically sound mice, characterized by shorter tumorigenesis time, larger tumor volume, severe bone destruction, and higher mortality. In conclusion, honeycomb-like porous microsphere scaffolds are constructed with uniform structure by microfluidic technology to massively produce tumor cells with original phenotypes. Those microspheres could recapitulate the physiology microenvironment of tumors, maintain cell-cell and cell-extracellular matrix interactions, and thus provide an effective and convenient strategy for tumor pathogenesis and drug screening research.

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“…Compared with favorable prognosis tumors, PC is characterized by its high degree of malignancy, insidious onset, no typical symptoms, many anatomical sites, low resection rate, high recurrence rate and poor prognosis. PC patients have an average 5-year survival rate of less than 10%, and less than 3% for patients with advanced or metastatic disease (Chen et al 2021). The incidence of PC continues to increase and there is an urgent need to improve survival rates.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Effects of Herbal Medicines in Pancreatic Cancer Through Modulation of Steroid Hormone Response Proteins

Zhang

Wang

Liu

et al. 2022

Preprint

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Many individual herbs and herbal formulae have been demonstrated to provide safe and effective treatment for Pancreatic cancer (PC); however, the therapeutic mechanisms underlying their effects have not been fully elucidated. A total of 114 herbal formulae comprising 216 single herbal medicines used to treat PC were identified. Cluster analysis revealed a core prescription including four herbs [Glycyrrhizae Radix et Rhizome (Gan Cao), Codonopsis Radix (Dang Shen), Citri Reticulatae Pericarpium (Chen Pi), and Pinelliae Rhizoma (Ban Xia)] in combination to treat PC, and 295, 256, 141, and 365 potential targets were screened for each of these four herbs, respectively. PC-related proteins (n = 2940) were identified from the DisGeNET database. Finally, 44 overlapping targets of herbs and PC were obtained, representing potential targets of the herbal medicines for PC treatment. GO enrichment analysis indicated that targets common to herbs and PC primarily functioned in response to steroid hormones. KEGG pathway enrichment analysis indicated that the herbs may prevent PC by influencing apoptotic, p53, and PI3K/Akt signaling pathways. Further, molecular docking analysis indicated that of identified bioactive compounds, stigmasterol, phaseol, perlolyrine, shinpterocarpin, and licopyranocoumarin have good binding ability with proteins involved in responses to steroid hormones, while stigmasterol, phaseol, perlolyrine, and DIOP have good binding ability with PTGS2(also known as COX-2), ESR1, ESR2, AR, and PGR. Conclusion: The anti-PC activity of herbal medicines may be mediated via regulation of proteins with roles in responses to steroid hormones. This study provides further evidence supporting the potential for use of herbal medicines to treat PC.

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Organoid model: A new hope for pancreatic cancer treatment?

Cited by 39 publications

References 76 publications

Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression

Autophagy-associated circRNA circATG7 facilitates autophagy and promotes pancreatic cancer progression

Honeycomb-Like Hydrogel Microspheres for 3D Bulk Construction of Tumor Models

Anticancer Effects of Herbal Medicines in Pancreatic Cancer Through Modulation of Steroid Hormone Response Proteins

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