An Advanced Orthotopic Ovarian Cancer Model in Mice for Therapeutic Trials

Zhang, Ying; Luo, Li; Zheng, Xueling; Yu, Tinghe

doi:10.1155/2016/2585787

Cited by 8 publications

(10 citation statements)

References 9 publications

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“…Orthotopic mouse ovarian cancer model was generated in nude mice (female, 6–8 weeks old) as previously described ( 12 ). Briefly, mice were anesthetized with pentobarbital, a 1.5 cm dorsal incision was performed in the kidney region, the left ovarian bursa was exposed and injected with 1×10 6 SKOV3/CDDP or SKOV3/CDDP/miR-199a-3p cells in 50 µl PBS (n=5/group).…”

Section: Methodsmentioning

confidence: 99%

miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8

Cui

Tian

et al. 2018

Oncol Rep

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Drug resistance remains a large obstacle for the treatment of ovarian cancer. miRNAs have been reported to be involved in cisplatin (CDDP) resistance in ovarian cancer. The aim of the present study was to investigate the function and mechanism of miR-199a-3p in the CDDP resistance in ovarian cancer. We found that miR-199a-3p was significantly downregulated in chemoresistant ovarian cancer tissues, as well as CDDP-resistant SKOV3/CDDP cells, compared to chemosensitive carcinomas and SKOV3 cells. Restoration of miR-199a-3p in SKOV3/CDDP cells reduced cell proliferation, G1 phase cell cycle arrest, cell invasion, and increased cell apoptosis, resulting in enhanced CDDP sensitivity, while miR-199a-3p inhibition resulted in the opposite effects. Luciferase reporter assay showed that integrin β8 (ITGB8), one of the integrins that is involved in the regulation of cell cycle and motility, was a direct target of miR-199a-3p. Overexpression of miR-199a-3p downregulated ITGB8 expression via binding to its 3′-UTR. In addition, overexpression of ITGB8 restored CDDP resistance inhibited by miR-199a-3p. Moreover, orthotopic ovarian cancer mouse model showed that miR-199a-3p enhanced CDDP sensitivity of ovarian cancer in vivo. Therefore, our results indicate that miR-199a-3p enhances CDDP sensitivity of ovarian cancer cells through downregulating ITGB8 expression, and miR-199a-3p may serve as a therapeutic target for the treatment of ovarian cancer patients with CDDP-resistance.

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Section: Methodsmentioning

confidence: 99%

miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8

Cui

Tian

et al. 2018

Oncol Rep

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“…A higher level of LC3-II in tumor tissues indicated that autophagy was involved in the anticancer effect. Efficacy of this modality should be validated in an orthotopic cancer model, considering limitations of an ectopic model (Zhang et al 2016(Zhang et al , 2017.…”

Section: :1mentioning

confidence: 99%

Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

Wan

Dai

Wang

et al. 2018

Endocrine-Related Cancer

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Clinical implications of the BRCA2 expression level on treatments of ovarian cancer are controversial. Here, we demonstrated that platinum-resistant cancer had a higher percentage of high BRCA2 level (87.5% vs 43.6%, = 0.001), and that patients with a low BRCA2 level in cancer tissues had longer progression-free survival (with a median time of 28.0 vs 12.0 months, < 0.001) and platinum-free duration (with a median time of 19.0 vs 5.0 months, < 0.001) compared with those with a high BRCA2 level. In human ovarian cancer cell lines CAOV-3 and ES-2, cisplatin induced an upregulation of the RAD51 protein, which was inhibited after silencing ; silencing enhanced the action of cisplatin and Knockdown of BRCA2 promoted cisplatin-induced autophagy. Interestingly, the autophagy blocker chloroquine enhanced cisplatin in BRCA2-silenced cells accompanied by an increase in apoptotic cells, which did not occur in BRCA2-intact cells; chloroquine enhanced the efficacy of cisplatin against BRCA2-silenced CAOV-3 tumors , with an increase in LC3-II level in tumor tissues. Sensitization of cisplatin was also observed in BRCA2-silenced CAOV-3 cells after inhibiting ATG7, confirming that chloroquine modulated the sensitivity via the autophagy pathway. These data suggest that a low BRCA2 level can predict better platinum sensitivity and prognosis, and that the modulation of autophagy can be a chemosensitizer for certain cancers.

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“…Tumor cells or a solid tumor are applicated intrabursally, i.e., into the bursa ovarica enclosing mouse ovary or directly onto the ovary, thereby reproducing the primary site of tumor growth and disease progression best [ 311 ]. Intrabursal as well as intraperitoneal inoculation allow tumor cells to spread throughout the peritoneal cavity and to attach to serosal surfaces thus representing a well-suited metastatic model [ 312 , 313 ]. It is, however, worth to consider that the bursal enclosure of mouse ovary does not apply to human ovary which restricts accurate imitation of metastasis.…”

Section: Mouse Models In Ovarian Cancer Researchmentioning

confidence: 99%

Modelling the Functions of Polo-Like Kinases in Mice and Their Applications as Cancer Targets with a Special Focus on Ovarian Cancer

Kressin

Fietz

Becker

et al. 2021

Cells

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Polo-like kinases (PLKs) belong to a five-membered family of highly conserved serine/threonine kinases (PLK1-5) that play differentiated and essential roles as key mitotic kinases and cell cycle regulators and with this in proliferation and cellular growth. Besides, evidence is accumulating for complex and vital non-mitotic functions of PLKs. Dysregulation of PLKs is widely associated with tumorigenesis and by this, PLKs have gained increasing significance as attractive targets in cancer with diagnostic, prognostic and therapeutic potential. PLK1 has proved to have strong clinical relevance as it was found to be over-expressed in different cancer types and linked to poor patient prognosis. Targeting the diverse functions of PLKs (tumor suppressor, oncogenic) are currently at the center of numerous investigations in particular with the inhibition of PLK1 and PLK4, respectively in multiple cancer trials. Functions of PLKs and the effects of their inhibition have been extensively studied in cancer cell culture models but information is rare on how these drugs affect benign tissues and organs. As a step further towards clinical application as cancer targets, mouse models therefore play a central role. Modelling PLK function in animal models, e.g., by gene disruption or by treatment with small molecule PLK inhibitors offers promising possibilities to unveil the biological significance of PLKs in cancer maintenance and progression and give important information on PLKs’ applicability as cancer targets. In this review we aim at summarizing the approaches of modelling PLK function in mice so far with a special glimpse on the significance of PLKs in ovarian cancer and of orthotopic cancer models used in this fatal malignancy.

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An Advanced Orthotopic Ovarian Cancer Model in Mice for Therapeutic Trials

Cited by 8 publications

References 9 publications

miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8

miR-199a-3p enhances cisplatin sensitivity of ovarian cancer cells by targeting ITGB8

Knockdown of BRCA2 enhances cisplatin and cisplatin-induced autophagy in ovarian cancer cells

Modelling the Functions of Polo-Like Kinases in Mice and Their Applications as Cancer Targets with a Special Focus on Ovarian Cancer

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