Page 47 - ARNM-3-3

Advances in Radiotherapy
& Nuclear Medicine PI3K and Akt in androgen-independent PCa

3.8. Correlation between AR and Akt expression survive under androgen-deprived conditions, leading to
in AIPC poor prognosis.
Spearman’s rank correlation analysis demonstrated a Regardless of disease stage – whether primary, metastatic,
positive correlation between AR and Akt expression in or AIPC – AR is positively expressed. Unfortunately, PCa
4-6
AIPC (correlation coefficient: R = 0.465; p=0.003 [p < eventually loses its dependence on androgen for growth,
0.05]). This indicates that Akt expression increases with and nearly all PCa patients will ultimately progress into
increasing AR expression intensity in AIPC (Table 6). AIPC. Although castration can suppress androgen activity,
it does not fully halt PCa progression. Therefore, abnormal
3.9. Correlation between PI3K and Akt expression activation of AR is considered a key driver in the onset and
in AIPC progression of AIPC, with the PI3K/Akt signaling pathway
Spearman’s rank correlation analysis showed a positive playing an important role in this process.
correlation between PI3K and Akt expression in AIPC The PI3K/Akt/mammalian target of rapamycin
(correlation coefficient: R = 0.421; p = 0.008 [p < 0.05]). (mTOR) pathway – also known as the threonine/serine
This finding suggests that the PI3K/Akt signaling pathway protein kinase (Akt or PKB) pathway – is considered a
plays a significant role in the transformation of ADPC into pivotal intracellular signaling pathway. Upon receiving
AIPC (Table 7).
extracellular signals, PI3K translocates to the plasma
4. Discussion membrane, where its substrate, phosphorylated to
phosphatidylinositol (3,4,5)-triphosphate (PIP3), is
ADT is typically effective in treating ADPC and remains the PIP3. The generation of PIP3 recruits Akt to the cell
primary treatment for PCa. However, after 18 – 24 months membrane, where it is activated through phosphorylation
of androgen suppression, ADT often becomes ineffective, by 3-phosphoinositide-dependent protein kinase-1.
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as tumor cells in AIPC gradually acquire the ability to Following activation, mTOR and Akt inhibit apoptosis
8
in precancerous cells, promote cancer cell survival,
Table 5. Relationship between androgen receptor and facilitate the progression of PCa. Notably, the PI3K
and phosphatidylinositol‑3‑kinase expression in 9
androgen‑independent prostate cancer pathway is significantly dysregulated in PCa.
Inactivation of the tumor suppressor gene PTEN is a
Molecular marker PI3K Correlation coefficient p‑value major cause of Akt pathway activation. Several studies
10
+ ++ +++ have shown that the AIPC characteristics of PCa are closely
AR associated with Akt activation. Murillo et al. found that
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+ 0 1 2 0.341 0.036 long-term culture of LNCaP cells in serum leads to sustained
++ 1 2 5 Akt activation and progression to an androgen-independent
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+++ 1 1 25 state. Malik et al. reported that activated Akt is strongly
Note: Positive staining intensities are denoted as “+” (weak positive), associated with the clinical characteristics of PCa.
“++” (medium positive), and “+++” (strong positive). Furthermore, research indicates that the proportion of
Abbreviations: ADPC: Androgen-dependent prostate cancer; activated Akt varies with tumor differentiation – it is highest
AIPC: Androgen-independent prostate cancer; AR: Androgen receptor;
PI3K: Phosphatidylinositol-3-kinase.
Table 7. Relationship between phosphatidylinositol‑3‑kinase
Table 6. Relationship between androgen receptor and Akt and protein kinase B expression in androgen‑independent
expression in androgen‑independent prostate cancer prostate cancer
Molecular marker Akt Correlation coefficient p‑value Molecular marker Akt Correlation p‑value
+ ++ +++ + ++ +++ coefficient
AR PI3K
+ 0 1 2 0.465 0.003 + 0 1 1 0.421 0.008
++ 0 2 6 ++ 0 1 3
+++ 0 0 27 +++ 0 1 31
Note: Positive staining intensities are denoted as “+” (weak positive), Note: Positive staining intensities are denoted as “+” (weak positive),
“++” (medium positive), and “+++” (strong positive). “++” (medium positive), and “+++” (strong positive).
Abbreviations: Akt: Protein kinase B; ADPC: Androgen-dependent Abbreviations: ADPC: Androgen-dependent prostate cancer; AIPC:
prostate cancer; AIPC: Androgen-independent prostate cancer; Androgen-independent prostate cancer; PI3K: Phosphatidylinositol-3-kinase.
AR: Androgen receptor.

Volume 3 Issue 3 (2025) 39 doi: 10.36922/ARNM025160018