We have previously demonstrated that CD44 variant 6 (CD44v6) is associated with prostate cancer (CaP) growth and therapeutic resistance in vitro, however, the role of CD44v6 in CaP in vivo is not fully understood. The purpose of this study is to investigate the effect of CD44v6 on CaP growth and chemo-/radiotherapy response in NOD/SCID mouse models in vivo and to validate its role as a therapeutic target for CaP therapy. CD44v6 was knocked down in PC-3M CaP cell line using short hairpin RNA. Subcutaneous (s.c.) and orthotopic CaP mouse xenografts were established. The effect of CD44v6 knockdown (KD) on tumour growth was evaluated in both s.c. and orthotopic models. Chemo-/radiotherapy response was evaluated in the s.c. model. Association of CD44v6 with PI3K/Akt pathway was validated using immunohistochemistry staining. We found that KD of CD44v6 significantly reduced tumour growth in both models, and enhanced the sensitivity of tumours to chemotherapy and radiotherapy in the s.c. model. In addition, we demonstrated that KD of CD44v6 is associated with downregulation of the PI3K/Akt/mTOR pathway. Our data confirm that CaP growth and chemo-/radiosensitivity in vivo is associated with CD44v6, which holds great promises as a therapeutic target in the treatment of CaP.

中文翻译：

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CD44变体6与体内前列腺癌的生长和化学/放射疗法的反应有关。

我们先前已证明CD44变体6（CD44v6）与体外前列腺癌（CaP）的生长和治疗耐药性相关，但是，CD44v6在CaP体内的作用尚不完全清楚。这项研究的目的是调查CD44v6在体内NOD / SCID小鼠模型中对CaP生长和化学/放疗反应的影响，并验证其作为CaP治疗的治疗靶标的作用。使用短发夹RNA在PC-3M CaP细胞系中敲除CD44v6。建立了皮下（sc）和原位CaP小鼠异种移植物。在sc和原位模型中均评估了CD44v6敲低（KD）对肿瘤生长的影响。在sc模型中评估化学疗法/放射疗法的反应。使用免疫组织化学染色验证了CD44v6与PI3K / Akt途径的关联。我们发现CD44v6的KD在两个模型中均显着降低了肿瘤的生长，并在sc模型中增强了肿瘤对化学疗法和放射疗法的敏感性。此外，我们证明了CD44v6的KD与PI3K / Akt / mTOR途径的下调有关。我们的数据证实，CaP的生长和体内的化学/放射敏感性与CD44v6有关，CD44v6具有广阔的前景，有望作为治疗CaP的治疗靶标。