Background

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most aggressive and lethal malignancies worldwide. Histone deacetylase 6 is a member of the histone deacetylase (HDAC) family that participates in histone acetylation and deacetylation and also targets several non-histone substrates to regulate cell proliferation, metastasis, invasion, and mitosis in tumors. Zebrafish have emerged as one powerful genetic model to study the developments in vertebrates. The study evaluates the HDAC6-I activity and its analog on a human pancreatic adenocarcinoma (PANC-1) cell line using a zebrafish xenograft model.

Methods

The human PANC-1 was implanted in peri-vitelline space (PVS) of 48-hour zebrafish embryos with Sirt6 inhibitor, Sirt6 analog, and without any of these two as control. Three days after the implant, the tumour’s area was measured using the ImageJ software. The number of cells undergoing metastasis was also evaluated. The human cell line PANC-1 was injected into the PVS of 48-hour-old zebrafish embryos.

Results

Three days after implantation, the tumor’s area increased significantly compared to day 0. In two other groups, the human cell line PANC-1 was injected with Sirt 6 inhibitor and Sirt6 analog in the PVS of 48-hour-old zebrafish embryos with Sirt6 inhibitor and Sirt6 analog. In both groups, tumor size regressed significantly (P<0.001) compared to the Control group. In both groups, lesser cells metastasized and moved to the tail part compared to the Control group.

Conclusions

This study suggests that the HDAC6-I and its analog have the potency to regress tumor size and reduce the number of cells undergoing metastasis. It paves a path for using these entities as therapeutic agents and calls for further research.