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J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 7 of 27

measurements. We showed that this induced tumor reoxygenation could benefit radiotherapy. Indeed, pre-
challenge of tumor-bearing mice with 7ACC2 considerably improved the anticancer efficacy of either single
high dose or fractionated low dose radiation therapy.

Conclusion: This study positions MPC as control point for lactate metabolism and expands on the anticancer
potential of MPC inhibition.

9. The anti-neoplastic effect of triiodothyronine on hepatocellular carcinoma is preceded by

reversion of the Warburg metabolism and inhibition of the pentose phosphate pathway

1
1
1
Andrea Perra , Marta Anna Kowalik , Lavinia Cabras , Silvia Giordano , Andrea Rasola ,
3
2
Amedeo Columbano 1
1 Department of Biomedical Sciences, University of Cagliari, Cagliari 09124, Italy.
2 Department of Biomedical Sciences, University of Padova, Padova 35122, Italy.
3 Department of Oncology, University of Torino, IRCCS Candiolo, Candiolo 10060, Italy.

Introduction: Liver carcinogenesis, from its very early steps, is characterized by reduced activation of thyroid
hormone nuclear receptors (THRs), and an altered glucose catabolism that leads to a Warburg metabolism
and a strong induction of the pentose phosphate pathway (PPP). The administration of the THRs agonist,
triiodothyronine (T3), reverts the preneoplastic hepatocytes to a fully differentiated phenotype and prevents
the development of hepatocellular carcinomas (HCC), but its effects on glucose metabolism have not yet been
fully explored. Given the strong link between THRs activation and metabolism, the aim of this study is to
verify whether T3 is able to restore the physiological PPP activity and energetic metabolism in neoplastic liver.

Experimental model: Rats were subjected to the Resistant-Hepatocyte model of liver carcinogenesis and
treated with T3 at 10 weeks, when preneoplastic nodules reached the maximal expansion, or at 10 months
after initiation, when HCCs appeared. Rats were killed after 4 or 7 days of T3 treatment.

Results: The treatment with T3 for 7 days resulted in a reduction in the number of preneoplastic lesions. This
effect was preceded by a change in the expression of key genes regulators of the glucose metabolism. The
immunohistochemical and enzymatic study of liver sections confirmed that the reversion of the Warburg
phenotype and inhibition of the PPP occurs before the disappearance of the preneoplastic lesions. The same
effect was evident also in fully developed HCCs.

Conclusion: Our results indicate that, at least in part, the antineoplastic effect of T3 depends on the ability of
the activated THRs to revert the Warburg phenotype together with an inhibition of the PPP.

2+
10. The interaction between the transcription factor STAT3 and the Ca channel IP3R3
2+
regulates Ca release from the endoplasmic reticulum and apoptosis

Lidia Avalle *, Annalisa Camporeale *, Giampaolo Morciano *, Elena Ghetti , Valeria Orecchia ,
2,
1,
1,
1
1
2
1,
2,
Carlotta Giorgi , Paolo Pinton *, Valeria Poli *
1 Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, 10126, Italy.
2 Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 44121, Italy.
*Equal contribution.