Abstract 1317
Background
The Jmjc-domain-containing protein 6 (JMJD6) is a member of JmjC oxygenases that contain both arginine demethylase and lysine hydroxylase activities. Overexpression of JMJD6 has been reported to be associated with the development of various types of cancers, such as breast, lung, liver, and colon cancer. The present study aimed to explore the inhibitory effect of the small-molecule JMJD6 inhibitor named WL8 obtained by virtual screening on the progression of colorectal cancer.
Methods
WL8 was administered to a mouse bearing xenografts of human colorectal cancer tissue, once every 7 days for 3 times. We analyzed the response of tumors from three patients to the JMJD6 inhibitor (11.5mg/kg, intrapertoneally, i.p.), and to FOLFOX (oxaliplatin 12mg/kg, calcium levifolinate 30mg/kg, 5-fluorouracil 55mg/kg, i.p.) or FOLFIRI (irinotecan 40mg/kg, calcium levifolinate 30mg/kg, 5-fluorouracil 55mg/kg, i.p.), as well as to combined usage of JMJD6 inhibitor and FOLFOX or FOLFIRI in PDX models by recording the tumors sizes every 3 or 4 days for 7 times. The differences between groups were analyzed using one-way ANOVA. (i.p. stands for intraperitoneal.).
Results
Compared with FOLFOX or FOLFIRI, WL8 inhibited tumor growth more effectively in the PDX models of three patients (One patient’s partial results are shown in the table). Combinatorial therapies using both JMJD6 and FOLFOX (or FOLFIRI) could further reduced the tumour size.Table: 632P
Group | 8 Days | 15 Days | 22 Days |
---|---|---|---|
Control | 1.8075±0.3950 $^@ | 2.5706±0.2900 #%$^@ | 2.6834±0.0416 #%$^@ |
FOLFOX | 1.4184±0.2067 | 1.3639±0.2381 *@ | 1.3867±0.4155 *^@ |
FOLFIRI | 1.4712±0.1568 | 1.3894±0.4543 *@ | 1.7474±0.0705 *$^@ |
WL8 | 0.9656±0.4456 * | 1.1069±0.4376 * | 1.1655±0.2884 *%^@ |
WL8+ FOLFOX | 0.7125±0.0410 *#% | 0.7767±0.4359 * | 0.4833±0.0503 *#%$ |
WL8+ FOLFIRI | 1.0325±0.3903* | 0.6367±0.1436 *#% | 0.3900±0.0265 *#%$ |
Relative tumor volumn (on days after first administration, notes: P values are indicated with symbols as follows, * P<0.05 v.s. ctrl; # P<0.05 v.s. FOLFOX; % P<0.05 v.s. FOFIRI; $ P<0.05 v.s. WL8; ^ P<0.05 v.s. WL8+FOLFOX; @ P<0.05 v.s. WL8+FOLFIRI)
Conclusions
We found an small-molecule inhibitor of JMJD6 with impressive therapeutic effects on colorectal cancer in pre-clinical study.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The First Affiliated Hospital of Xiamen University.
Funding
National Natural Science Foundation of China, Fujian Provincial Department of Science and Technology, Fujian Provincial Health and Family Planning Commission Foundation of Youth Scientific Research Project, Xiamen Science and Technology Bureau Foundation of Science and Technology Project for the Benefit of the People.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3006 - Nal-iri/lv5-fu versus paclitaxel as second-line therapy in patients with metastatic esophageal squamous cell carcinoma (OESIRI-PRODIGE 62): A FFCD multicenter, randomized, phase II study.
Presenter: Violaine Randrian
Session: Poster Display session 2
Resources:
Abstract
3697 - The expression of Versican and its role in pancreatic neuroendocrine tumor
Presenter: Zhao Sun
Session: Poster Display session 2
Resources:
Abstract
6073 - Characteristics of patients with thyroid carcinoma in the united states
Presenter: Dina El-Habashy
Session: Poster Display session 2
Resources:
Abstract
2124 - The discrimination of pituitary adenomas and craniopharyngioma on MRI: from image features to texture features
Presenter: Hanyue Xu
Session: Poster Display session 2
Resources:
Abstract
3786 - Proportion of Peripheral Lymphocyte Subsets Correlates with the Progression-free Survival and Metastatic Status of Pancreatic Neuroendocrine Tumor Patients
Presenter: Yitao Gong
Session: Poster Display session 2
Resources:
Abstract
2263 - Immunohistochemical expression of ER-α and PR in papillary thyroid carcinoma
Presenter: Enas Elkhouly
Session: Poster Display session 2
Resources:
Abstract
4386 - SILVELUL Project: Immunohistochemical panel analyses as potential predictive and prognostic factors in Pancreatic Neuroendocrine Tumors (PanNET) Treated with CAPTEM or Everolimus
Presenter: Ana De Jesus-Acosta
Session: Poster Display session 2
Resources:
Abstract
2302 - Carcinoid heart disease (CHD): the CRUSOE-NETs, a prospective cohort study from the French Group of Endocrine Tumors (GTE)
Presenter: Kathleen Dekeister Geoffroy
Session: Poster Display session 2
Resources:
Abstract
5749 - Safety of high doses of somatostatin analogs in well differentiated NENs in elderly
Presenter: Massimiliano Cani
Session: Poster Display session 2
Resources:
Abstract
3931 - Differences in multikinase inhibitors (MKI) toxicity profile according to gender. A pooled analysis of three phase II trials with lenvatinib, pazopanib and sorafenib in patients (pts) with advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs).
Presenter: Jorge Hernando Cubero
Session: Poster Display session 2
Resources:
Abstract